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OBJECTIVE: Racially minoritized youth with T1D are made vulnerable to disproportionately adverse health outcomes compared to White peers due to enduring systems of oppression. Thus, understanding modifiable psychosocial factors associated with diabetes-related outcomes in racially minoritized youth may help to buffer deleterious effects of racism. One factor meriting exploration is racial-ethnic identity. There is currently limited research on measures fit to assess ethnic identity in youth with chronic illnesses. This study's purpose is to examine the factor structure, reliability, and validity of the revised Multigroup Ethnic Identity Measure (MEIM-R) in a racially- and income-diverse sample of youth with T1D across sociodemographic and illness-related proxies for one's positionality in oppressive systems. METHOD: As part of a larger study examining resilience, 142 youth with T1D ages 12-18 (Mage = 14.66, SDage = 1.62, 55.6% Black/African-American, 44.4% White) completed the MEIM-R and various psychosocial measures. HbA1c levels and illness duration were extracted from medical records and caregivers reported income information. Confirmatory factor analyses compared the structural validity of competing MEIM-R models, and uniform and non-uniform differential item functioning (DIF) was explored across sociodemographic and illness-related factors. RESULTS: While a bifactor structure was supported, the MEIM-R was found to exhibit DIF by race and gender on multiple MEIM-R items and did not demonstrate linear bivariate relations with other psychosocial factors. CONCLUSIONS: Since different MEIM-R item response patterns were observed across racial/ethnic and gender groups, caution is warranted in using this measure in racially and gender diverse youth with T1D.
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BACKGROUND: There is limited understanding of associations between a combination of health behaviors (physical activity, sedentary/screen-time, diet) and cardiometabolic health risk factors, physical performance, and emotional health among young (<18) childhood cancer survivors (CCS). The aims of this research were to address this gap by 1) deriving health behavior adherence profiles among CCS, and 2) examining associations among demographic, diagnosis and/or treatment exposures, cardiometabolic, physical performance, and emotional functioning with health behavior profile membership. METHODS: Participants included 397 CCS (≥5 years post-diagnosis; 10-17 years old) enrolled in the St. Jude Lifetime Cohort Study who completed physical health evaluations and questionnaires assessing health behaviors and psychological functioning. Latent profile analysis was used to derive profiles of health behavior adherence. Logistic regression and t-tests were used to examine mean-level differences and associations between profile membership with demographic, diagnosis, treatment exposures, cardiometabolic health, psychological functioning, and physical performance. RESULTS: Two profiles emerged: inactive-unhealthy-diet ("IU") and active-sedentary-unhealthy-diet ("ASU") to guidelines. More participants in IU demonstrated higher resting heart rate (mean [M], 76.54; SD = 12.00) and lower motor proficiency scores (M = 34.73; SD = 29.15) compared to ASU (resting heart rate, M = 71.95, SD = 10.74; motor proficiency, M = 50.40, SD = 31.02). CONCLUSIONS: CCS exhibited low adherence to multiple health behavior guidelines, with adherence patterns differentially associated with cardiometabolic health (i.e., resting heart rate) and physical performance. However, robust protection against all health variables was not observed. Findings suggest interventions designed to improve health outcomes should target multiple health behaviors simultaneously. PLAIN LANGUAGE SUMMARY: Pediatric cancer survivors are at-risk for detrimental health outcomes associated with cancer and treatment. Engagement in healthy lifestyle behaviors serves to reduce health vulnerabilities among adult survivors but less is known about associations with lifestyle behaviors on young survivors. This study documents patterns of lifestyle behaviors among survivors of pediatric cancer, factors that increase susceptibility to nonadherence, and associations among lifestyle behaviors and health indicators.
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Sobreviventes de Câncer , Doenças Cardiovasculares , Neoplasias , Humanos , Criança , Adolescente , Estudos de Coortes , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/psicologia , Sobreviventes , Comportamentos Relacionados com a SaúdeRESUMO
BACKGROUND: There is limited evidence evaluating the impact of insulin treatment strategies on glucose variability in critically ill patients without preexisting diabetes. OBJECTIVE: Compare basal plus insulin (BPI) and sliding scale insulin (SSI) impact on glycemic control outcomes in critically ill patients without preexisting diabetes experiencing hyperglycemia. METHODS: This multicenter, retrospective review analyzed critically ill patients with hyperglycemia who received either BPI or SSI. Patients with a hemoglobin A1C >6.5% during the admission of interest or in the previous 3 months, or a diagnosis of diabetes at the time of discharge were excluded. The primary outcome was glucose variability during the intensive care unit (ICU) admission. Secondary outcomes included hypoglycemia frequency, frequency of goal glucose levels, mortality, and length of stay. RESULTS: The analysis included 228 patients (39 in BPI, 189 in SSI). Average glucose variability was higher in the BPI group compared with the SSI group (85.8 mg/dL ± 33.1 vs 70.2 mg/dL ± 30.7; P = 0.009), which remained when controlling for baseline confounding (-12.1 [5.6], 95% CI -23.2 to -0.99; P = 0.033). Hypoglycemia incidence was similar between groups. BPI patients had a lower incidence of glucose values within goal range than SSI patients (P = 0.046). There was no difference in length of stay or hospital mortality. CONCLUSIONS AND RELEVANCE: The use of SSI compared with a BPI regimen may result in reduced glycemic variability in critically ill patients without preexisting diabetes. Future prospective studies, with a larger sample size, are warranted to confirm our exploratory findings and characterize clinically significant benefits.
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OBJECTIVE: The aim of this study was to identify patterns of distress and growth in parents of children with cancer and examine associations with subsequent parenting, parent-child relationship, and family environment. METHODS: Participants included children with cancer history (8-17 years) stratified by time since diagnosis and their parent. At enrollment, parents (n = 254) reported depression and anxiety, and post-traumatic stress symptoms, posttraumatic growth (PTG), and benefit finding in relation to their child's cancer. Three years later, children (n = 214) reported parenting behavior, parent reactions to their distress, and family environment. Parents reported their reaction to children's distress and qualities of the parent-child relationship. RESULTS: Latent profile analysis empirically identified 3 cross-sectional profiles using baseline data: "Resilience, High Growth" (50%), characterized by the lowest distress and the highest PTG/benefit finding; "Moderate Distress with Growth" (33%), characterized by relatively high levels of all indicators; and "Resilience, Low Growth" (17%), characterized by relatively low distress with low PTG/benefit finding. Membership in profiles was associated with parent gender; parents' stressful life events; socioeconomic status; and child diagnosis, on versus off treatment status, and treatment intensity. Parent membership in the Moderate Distress with Growth profile was generally linked with poorer parenting behavior, parent-child relationship quality, and family functioning. CONCLUSION: The majority of parents exhibited resilience and growth. However, a subset of parents displaying moderate distress may be at risk for subsequent parenting and family functioning challenges. Findings further highlight the importance of screening for even moderate parent distress and the possible impact of parent psychosocial interventions indirectly on parenting and family functioning.
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Neoplasias , Crescimento Psicológico Pós-Traumático , Humanos , Poder Familiar/psicologia , Estudos Transversais , Pais/psicologia , Neoplasias/psicologiaRESUMO
OBJECTIVE: The role of transition-focused psychology appointments in managing the transition off therapy is unclear. The objective of this research was to explore caregiver perceived familial distress and the role of psychology in preparing families for transition. METHODS: Fifty-seven caregivers of youth, who finished treatment, completed an online questionnaire through a quality improvement project on experiences of families at transition. Twenty-two percent of caregivers had children who completed a transition-focused psychology consult and 63% completed a cognitive assessment at transition. Retrospective analyses were conducted assessing the association of psychology visits on caregiver perceptions of being informed of and prepared to manage transition-related challenges. RESULTS: Most caregivers reported experiencing adjustment concerns for family members. Caregivers of children completing a transition-focused psychology consult or cognitive assessment reported feeling more informed and greater preparedness to manage difficulties. Although decreased distress was not associated with the visit, those who felt more informed and prepared reported lower distress. CONCLUSIONS: Caregivers perceive transitioning off therapy as stressful for their family, though they experience decreased familial distress when informed of and prepared to manage transition-related challenges. These findings highlight the importance of psychosocial support at transition.
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Cuidadores , Neoplasias , Adolescente , Cuidadores/psicologia , Criança , Família/psicologia , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.
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Desenvolvimento Fetal , Saúde Materna , Estresse Fisiológico , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Resultado da Gravidez , Razão de MasculinidadeRESUMO
The use of microalgal biomass for metal pollutant bioremediation might be improved by genetic engineering to modify the selectivity or capacity of metal biosorption. A plant cadmium (Cd) and zinc (Zn) transporter (AtHMA4) was used as a transgene to increase the ability of Chlamydomonas reinhardtii to tolerate 0.2 mM Cd and 0.3 mM Zn exposure. The transgenic cells showed increased accumulation and internalization of both metals compared to wild-type. AtHMA4 was expressed either as the full-length (FL) protein or just the C-terminal (CT) tail, which is known to have metal-binding sites. Similar Cd and Zn tolerance and accumulation was observed with expression of either the FL protein or CT domain, suggesting that enhanced metal tolerance was mainly due to increased metal binding rather than metal transport. The effectiveness of the transgenic cells was further examined by immobilization in calcium alginate to generate microalgal beads that could be added to a metal contaminated solution. Immobilization maintained metal tolerance, while AtHMA4-expressing cells in alginate showed a concentration-dependent increase in metal biosorption that was significantly greater than alginate beads composed of wild-type cells. This demonstrates that expressing AtHMA4 FL or CT has great potential as a strategy for bioremediation using microalgal biomass.
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Adenosina Trifosfatases/genética , Proteínas de Arabidopsis/genética , Bioacumulação , Cádmio/metabolismo , Chlamydomonas reinhardtii/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Transgenes , Zinco/metabolismo , Adenosina Trifosfatases/metabolismo , Proteínas de Arabidopsis/metabolismo , Biodegradação Ambiental , Transporte Biológico , Chlamydomonas reinhardtii/genéticaRESUMO
Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.
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Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Estresse Psicológico/epidemiologia , Adulto , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Percepção , Pré-Eclâmpsia/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: Glucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk. METHODS: This is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery. RESULTS: Biochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement. CONCLUSIONS: We demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.
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Insuficiência Adrenal/induzido quimicamente , Glucocorticoides/efeitos adversos , Nefropatias/tratamento farmacológico , Prednisolona/efeitos adversos , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Biomarcadores/sangue , Cosintropina/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Nefropatias/sangue , Glomérulos Renais , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Prednisolona/administração & dosagem , Curva ROC , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Inflammatory breast cancer (IBC) often affects women at a relatively young age. To the authors' knowledge, the rate of BRCA variants among patients with IBC is not known. To determine the association between BRCA status and IBC, the authors evaluated its rate and compared the clinicopathologic characteristics of patients with IBC with those of patients with other breast cancers (non-IBC). METHODS: Patients who presented at the study institution's cancer genetics program and who underwent BRCA genetic testing were included in the current study. The authors compared clinicopathologic data between patients with IBC and those with non-IBC using propensity score matching to identify predictors. RESULTS: A total of 1789 patients who underwent BRCA genetic testing (1684 with non-IBC and 105 with IBC) were included. BRCA pathogenic variants were found in 27.3% of patients with non-IBC and 18.1% of patients with IBC (P = .0384). After propensity score matching, there were no significant differences noted between patients with IBC and those with non-IBC, including the rate of BRCA pathogenic variants (P = .5485). However, a subgroup analysis of the 479 patients with BRCA pathogenic variants demonstrated that patients with IBC (19 patients) were diagnosed at significantly younger ages compared with patients with non-IBC (P = .0244). CONCLUSIONS: There was no clear association observed between BRCA pathogenic variants and IBC. However, among patients who tested positive for BRCA pathogenic variants, those with IBC were younger at the time of diagnosis compared with those with non-IBC breast cancers. These results confirm that genetic testing is important for patients with IBC who meet the current clinical criteria for genetic testing in breast cancer. Cancer 2018;124:466-74. © 2017 American Cancer Society.
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Genes BRCA1 , Genes BRCA2 , Neoplasias Inflamatórias Mamárias/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Testes Genéticos , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Pessoa de Meia-Idade , Pontuação de PropensãoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. AIM: The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. DESIGN: This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40weeks of treatment with spironolactone 25mg once daily to chlorthalidone 25mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40weeks of randomly allocated drug therapy and at 46weeks after discontinuation of the study drug.
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Clortalidona/administração & dosagem , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/complicações , Espironolactona/administração & dosagem , Adulto , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/mortalidade , Hipertrofia Ventricular Esquerda/fisiopatologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Análise de Onda de Pulso , Método Simples-Cego , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Rigidez VascularRESUMO
Many eukaryotic microalgae modify their metabolism in response to nutrient stresses such as phosphorus (P) starvation, which substantially induces storage metabolite biosynthesis, but the genetic mechanisms regulating this response are poorly understood. Here, we show that P starvation-induced lipid and starch accumulation is inhibited in a Chlamydomonas reinhardtii mutant lacking the transcription factor Pi Starvation Response1 (PSR1). Transcriptomic analysis identified specific metabolism transcripts that are induced by P starvation but misregulated in the psr1 mutant. These include transcripts for starch and triacylglycerol synthesis but also transcripts for photosynthesis-, redox-, and stress signaling-related proteins. To further examine the role of PSR1 in regulating lipid and starch metabolism, PSR1 complementation lines in the psr1 strain and PSR1 overexpression lines in a cell wall-deficient strain were generated. PSR1 expression in the psr1 lines was shown to be functional due to rescue of the psr1 phenotype. PSR1 overexpression lines exhibited increased starch content and number of starch granules per cell, which correlated with a higher expression of specific starch metabolism genes but reduced neutral lipid content. Furthermore, this phenotype was consistent in the presence and absence of acetate. Together, these results identify a key transcriptional regulator in global metabolism and demonstrate transcriptional engineering in microalgae to modulate starch biosynthesis.
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Chlamydomonas reinhardtii/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/metabolismo , Fósforo/metabolismo , Proteínas de Plantas/metabolismo , Carbono/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/ultraestrutura , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Genes de Plantas , Teste de Complementação Genética , Metabolismo dos Lipídeos/genética , Modelos Biológicos , Mutação , Proteínas Nucleares/genética , Proteínas de Plantas/genética , Amido/metabolismoRESUMO
OBJECTIVE: Most prolactinomas in females are diagnosed during the reproductive age, and the majority are microadenomas. Prolactinomas detected in the postmenopausal period are less common with limited published data on their presentation and prognosis. Our objective was to assess the presenting clinical, biochemical and imaging findings, as well as the outcomes of women diagnosed with a prolactinoma in the postmenopausal period. DESIGN AND METHODS: We undertook a retrospective cohort study of women diagnosed with prolactinoma after menopause and followed up in a large UK pituitary centre. Information on presentation, management and outcomes was collected. RESULTS: Seventeen women with a median age at diagnosis of 63 years (range 52-78) were identified. Headaches and/or visual deterioration were the most commonly reported complaints at detection of the adenoma (47%). Acute pituitary apoplexy was diagnosed at presentation or during follow-up in 18% of the cases. The median serum prolactin was 12 364 mU/L (range 2533-238 479). Macroprolactinomas comprised 94% of the tumours, and 88% of them had supra/parasellar extension. All patients with macroprolactinoma were offered dopamine agonist, and normal prolactin was achieved in 94% of them (median follow-up 91.5 months). Adenoma shrinkage was observed in all women. Improvement or resolution of visual disturbances documented at presentation was observed in 86% of cases. CONCLUSIONS: The clinical phenotype of prolactinomas diagnosed in the postmenopausal period is characterized by dominance of macroadenomas, with frequent supra/parasellar extension and a relative high rate of acute pituitary apoplexy. In this group of patients, the response of the macroadenomas to dopamine agonists is good.
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Pós-Menopausa , Prolactinoma/diagnóstico , Idoso , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Fenótipo , Apoplexia Hipofisária , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Transtornos da VisãoRESUMO
Carica papaya (papaya) seed germinate readily fresh from the fruit, but desiccation induces a dormant state. Dormancy can be released by exposure of the hydrated seed to a pulse of elevated temperature, typical of that encountered in its tropical habitat. Carica papaya is one of only a few species known to germinate in response to heat shock (HS) and we know little of the mechanisms that control germination in tropical ecosystems. Here we investigate the mechanisms that mediate HS-induced stimulation of germination in pre-dried and re-imbibed papaya seed. Exogenous gibberellic acid (GA3 ≥250 µM) overcame the requirement for HS to initiate germination. However, HS did not sensitise seeds to GA3, indicative that it may act independently of GA biosynthesis. Seed coat removal also overcame desiccation-imposed dormancy, indicative that resistance to radicle emergence is coat-imposed. Morphological and biomechanical studies identified that neither desiccation nor HS alter the physical structure or the mechanical strength of the seed coat. However, cycloheximide prevented both seed coat weakening and germination, implicating a requirement for de novo protein synthesis in both processes. The germination antagonist abscisic acid prevented radicle emergence but had no effect on papaya seed coat weakening. Desiccation therefore appears to reduce embryo growth potential, which is reversed by HS, without physically altering the mechanical properties of the seed coat. The ability to germinate in response to a HS may confer a competitive advantage to C. papaya, an opportunistic pioneer species, through detection of canopy removal in tropical forests.
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Carica/metabolismo , Germinação/fisiologia , Resposta ao Choque Térmico/fisiologia , Sementes/metabolismo , Carica/fisiologia , Cicloeximida/farmacologia , Desidratação , Germinação/efeitos dos fármacos , Giberelinas/farmacologia , Temperatura Alta , Dormência de Plantas/efeitos dos fármacos , Dormência de Plantas/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Sementes/fisiologiaRESUMO
BACKGROUND AND AIMS: GPT2, a glucose 6-phosphate/phosphate translocator, plays an important role in environmental sensing in mature leaves of Arabidopsis thaliana. Its expression has also been detected in arabidopsis seeds and seedlings. In order to examine the role of this protein early in development, germination and seedling growth were studied. METHODS: Germination, greening and establishment of seedlings were monitored in both wild-type Arabidopsis thaliana and in a gpt2 T-DNA insertion knockout line. Seeds were sown on agar plates in the presence or absence of glucose and abscisic acid. Relative expression of GPT2 in seedlings was measured using quantitative PCR. KEY RESULTS: Plants lacking GPT2 expression were delayed (25-40 %) in seedling establishment, specifically in the process of cotyledon greening (rather than germination). This phenotype could not be rescued by glucose in the growth medium, with greening being hypersensitive to glucose. Germination itself was, however, hyposensitive to glucose in the gpt2 mutant. CONCLUSIONS: The expression of GPT2 modulates seedling development and plays a crucial role in determining the response of seedlings to exogenous sugars during their establishment. This allows us to conclude that endogenous sugar signals function in controlling germination and the transition from heterotrophic to autotrophic growth, and that the partitioning of glucose 6-phosphate, or related metabolites, between the cytosol and the plastid modulates these developmental responses.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Regulação Enzimológica da Expressão Gênica , Glucose-6-Fosfato/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Transdução de Sinais , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Cloroplastos/genética , Cotilédone/genética , Cotilédone/crescimento & desenvolvimento , Cotilédone/fisiologia , Regulação da Expressão Gênica de Plantas , Germinação , Glucose/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Mutagênese Insercional , Fenótipo , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/fisiologiaRESUMO
BACKGROUND: Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis. Antibiotics are widely used, but the pharmacokinetics of these agents are unknown as is their efficacy. We wished to assess the perfusate concentrations of the meropenem and fluconazole that we use and to audit the incidence of infection with this antimicrobial therapy. METHODS: Fluconazole and meropenem (100 mg each) were added to the perfusate before NMP began, and serial samples were taken and assayed for drug concentrations. Perfusate cultures were available from 210 of the 242 perfusions performed between February 1, 2018, and April 6, 2023; these were reviewed. RESULTS: Following administration of 100 mg fluconazole, levels fell slightly from a median of 24.9 mg/L at 1 h to 22.6 mg/L at 10 h. In contrast, meropenem concentrations fell over time, from a median of 21.8 mg/L at 1 h to 9.4 mg/L at 10 h. There were 4 significant microorganisms grown in the perfusions, including 3 Candida species and an Enterococcus faecium . All the Candida -infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the Enterococcus -infected liver was not transplanted. CONCLUSIONS: Serious infection is a risk with NMP but appears to be mitigated with a protocol combining fluconazole and meropenem. This combination may not be appropriate in areas where resistance is prevalent. Routine culture of NMP perfusate is essential to identify breakthrough organisms early and enable recipient treatment.
Assuntos
Fluconazol , Transplante de Fígado , Meropeném , Perfusão , Humanos , Meropeném/farmacocinética , Meropeném/administração & dosagem , Transplante de Fígado/efeitos adversos , Fluconazol/farmacocinética , Fluconazol/administração & dosagem , Incidência , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Preservação de Órgãos/métodos , Antibioticoprofilaxia/métodos , Estudos Retrospectivos , Fígado/metabolismo , Fígado/microbiologia , Fígado/efeitos dos fármacos , Candidíase/epidemiologia , Candidíase/prevenção & controle , Candidíase/tratamento farmacológico , Candidíase/diagnósticoRESUMO
PURPOSE: Complementary and integrative medicine (CIM) therapies (i.e., non-conventional Western medicine interventions) may reduce side-effects associated with pediatric oncology treatment. CIM therapies may also improve caregiver psychological and physical health that is exacerbated during pediatric cancer treatment. Despite known benefits, these therapies are not widely used within pediatric oncology populations in the United States. To guide and promote CIM use among this population, the aim of this project was to qualitatively explore factors that contribute to caregivers' decision to include CIM use in their own and child's care. METHODS: Twenty caregivers of children (ages 0.5-14 years) being treated for cancer participated in this study. Each completed a demographic form and the CIM use questionnaire. Qualitative interviews followed by a card sort task were used to assess barriers and facilitators of uptake for caregivers and their child with cancer. RESULTS: A number of predisposing (e.g., child age, beliefs) and needs factors (e.g., potential to treatment-related side-effects) provide insight into caregivers' decisions to use CIM for their child. Analyses also revealed the importance of enabling factors (e.g., resources) for caregiver use. Caregivers also reported benefiting from additional information about risk/benefit analysis of these therapies, and current research for CIM use in caregivers and children being treated for cancer. CONCLUSION: Children may benefit from individually tailored complementary and integrative medicine consultations that explore patient history and specific needs factors to improve preference concordant care and uptake. Caregivers may benefit from support that improves enabling factors associated with care (e.g., improved accessibility).
Assuntos
Cuidadores , Terapias Complementares , Medicina Integrativa , Neoplasias , Pesquisa Qualitativa , Humanos , Criança , Terapias Complementares/métodos , Masculino , Feminino , Adolescente , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Cuidadores/psicologia , Pré-Escolar , Lactente , Adulto , Tomada de Decisões , Inquéritos e Questionários , Pessoa de Meia-Idade , Estados UnidosRESUMO
PURPOSE: Perceived cancer impact (PCI) is the degree to which one feels cancer has impacted one's life. It is unknown if PCI is associated with health behaviors. The aim of this study is to determine associations between PCI and health behaviors in childhood cancer survivors. METHODS: Participants were ≥ 5-year survivors enrolled in the St. Jude Lifetime (SJLIFE) cohort. The Brief Cancer Impact (BCIA) assessed PCI across four domains (caregiving/finances, diet/exercise, social/emotional functioning, religiosity). Responses were categorized as negative, neutral, or positive impact. Smoking, risky drinking, illicit drug use, and diet quality data were obtained via self-report. Physical activity (PA) was assessed via self-report and actigraphy. Cross-sectional and longitudinal associations between PCI and health behaviors were evaluated via multivariable logistic regression. RESULTS: A total of 3623 participants (mean age 30.4 ± 8.3 years, 49.6% female, 81.5% NH White) were included in baseline cross-sectional analysis; 1709 had a second visit 5.0 ± 1.4 years later and were included in longitudinal analysis. At baseline, the percentage of participants who endorsed cancer as having a negative impact on caregiving/finances was 37.5%, diet/exercise 30.5%, social/emotional functioning 40.6%, and religiosity 8.7%. Negative and neutral PCI across all four domains were cross-sectionally associated with all behaviors except illicit drug use. Negative and neutral PCI at the first time point across all four domains were associated with smoking, diet quality, and PA (ORs ranging from 1.35 to 2.41) in longitudinal analyses. CONCLUSIONS: Endorsing negative or neutral PCI is associated with adverse health behaviors. IMPLICATIONS FOR CANCER SURVIVORS: Promoting optimal health behavior should include addressing PCI.
RESUMO
BACKGROUND: Normothermic ex situ liver perfusion (NESLiP) has the potential to increase organ utilization. Radiological evidence of localized liver injury due to compression at the time of NESLiP, termed cradle compression, is a recognized phenomenon but is poorly characterized. METHODS: A retrospective analysis of a prospectively collected database was performed of transplanted livers that underwent NESLiP and subsequently had a computed tomography performed within the first 14 d posttransplant. The primary study outcome was 1-y graft survival. RESULTS: Seventy livers (63%) were included in the analysis. Radiological evidence of cradle compression was observed in 21 of 70 (30%). There was no difference in rate of cradle compression between donor after circulatory death and donated after brain death donors ( P â =â 0.37) or with duration of NESLiP. Univariate analysis demonstrated younger (area under the receiver operating characteristic, 0.68; P = 0.008; 95% confidence interval [CI], 0.55-0.82) and heavier (area under the receiver operating characteristic, 0.80; P â <â 0.001; 95% CI, 0.69-0.91) livers to be at risk of cradle compression. Only liver weight was associated with cradle compression on multivariate analysis (odds ratio, 1.003; P â =â 0.005; 95% CI, 1.001-1.005). There was no difference in 1-y graft survival (16/17 [94.1%] versus 44/48 [91.6%]; odds ratio, 0.69; P â =â 0.75; 95% CI, 0.07-6.62). CONCLUSIONS: This is the first study assessing the impact of cradle compression on outcome. We have identified increased donor liver weight and younger age as risk factors for the development of this phenomenon. Increasing utilization of NESLiP will result in the increased incidence of cradle compression but the apparent absence of long-term sequelae is reassuring. Routine postoperative axial imaging may be warranted.
Assuntos
Sobrevivência de Enxerto , Transplante de Fígado , Fígado , Perfusão , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Masculino , Perfusão/métodos , Perfusão/efeitos adversos , Feminino , Pessoa de Meia-Idade , Fígado/diagnóstico por imagem , Fígado/irrigação sanguínea , Fígado/patologia , Adulto , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Preservação de Órgãos/métodos , Preservação de Órgãos/efeitos adversos , Análise Multivariada , Idoso , Doadores de Tecidos , Tamanho do ÓrgãoRESUMO
BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.