RESUMO
Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.
Assuntos
Ácidos Graxos , Glucose , Coração , Leite Humano , Ácido gama-Linolênico , Feminino , Humanos , Recém-Nascido , Gravidez , Cromatina/genética , Ácidos Graxos/metabolismo , Ácido gama-Linolênico/metabolismo , Ácido gama-Linolênico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Coração/efeitos dos fármacos , Coração/embriologia , Coração/crescimento & desenvolvimento , Homeostase , Técnicas In Vitro , Leite Humano/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Receptores X de Retinoides/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND AND PURPOSE: Pain is a common condition among people with hemophilia (PWH), negatively impacting quality of life. However, effective treatment remains a challenge. This two-arm, parallel randomized controlled pilot trial aimed to examine the three-month effects of hypnosis intervention on clinical and psychosocial variables, and on the inflammatory profile of PWH. MATERIALS AND METHODS: The study was conducted between January and October 2018, in a Reference Center for Congenital Coagulopathies. Adult (age ≥18) patients were randomized to experimental group (EG) or control group (CG). The EG received four weekly hypnosis sessions plus treatment-as-usual, and the CG maintained treatment-as-usual only. Outcomes were evaluated at one week and three months post-intervention and included pain, joint status, health-related quality of life (HRQoL), emotional state and inflammatory profile (leukocytes, C-reactive protein, cytokines). The randomization sequence was computer-generated, and allocation was concealed until enrolment. The outcome assessor was blind to allocation, but blinding of the participants was not possible due to the differences in procedure. RESULTS: Twenty patients were randomized to EG (n = 10; 8 analyzed) or CG (n = 10; 10 analyzed). Two-way mixed ANOVA showed significant time × group interactions on pain interference with normal work and with relations with other people, and on perception of health status. The EG significantly improved in pain interference with normal work and perception of health status. There was no report of harm. CONCLUSION: Hypnosis may be a promising intervention to manage hemophilia-related pain and promote HRQoL, with benefits lasting up to three months.
Assuntos
Hemofilia A , Hipnose , Adulto , Hemofilia A/terapia , Humanos , Dor/etiologia , Projetos Piloto , Qualidade de VidaRESUMO
BACKGROUND: Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. METHODS: This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). CONCLUSIONS: SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.
Assuntos
Compostos Férricos , Hiperfosfatemia , Insuficiência Renal Crônica , Sacarose , Adolescente , Criança , Combinação de Medicamentos , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Fósforo , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Joint deterioration and associated chronic pain are common among people with haemophilia (PWH), having an impact on quality-of-life. Though non-pharmacological strategies are recommended, psychological interventions to promote pain control and quality-of-life have scarcely been tested in haemophilia. This randomised controlled pilot trial aimed to assess feasibility, acceptability and effectiveness of hypnosis for pain management and promotion of health-related quality-of-life (HRQoL) among PWH. Twenty adults were randomised either to four weekly hypnosis sessions plus treatment-as-usual (experimental group; EG) or treatment-as-usual only (control group; CG). Participants completed sociodemographic and clinical assessment, measures of pain, HRQoL and emotional distress before (T1) and after (T2) intervention. Changes were analysed by calculating the differences between T1 and T2, and the groups were compared through independent-sample t tests (or chi-squared). Retention rates (90%) and analysis of patient satisfaction showed good acceptability and feasibility of the intervention. The EG (n = 8) had a higher reduction on pain interference than the CG (n = 10) (d = -0.267). A higher improvement on HRQoL (EQ-5D index: d = 0.334; EQ-5D VAS: d = 1.437) and a tendency towards better haemophilia-related quality-of-life (A36-Hemofilia QoL) were also evident in the EG. This is the first study showing the effectiveness of hypnosis to reduce pain interference and promote HRQoL among PWH.
Assuntos
Promoção da Saúde , Hemofilia A/complicações , Hipnose/métodos , Manejo da Dor , Dor/prevenção & controle , Qualidade de Vida , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Satisfação do PacienteRESUMO
Breast cancer is the most common type of cancer for women and is associated with increased distress. Spirituality and posttraumatic growth (PTG) have been associated with illness adjustment, but the relationship between these variables is still not well understood. A sample of 100 breast cancer patients completed a demographic and clinical questionnaire, the Posttraumatic Growth Inventory, Spiritual and Religious Attitudes in Dealing with Illness, and the Hospital Anxiety and Depression Scale. Results showed an association between PTG, spirituality and distress. Women with a longer diagnosis and recurrence showed more distress. Younger age, recurrent cancer and spirituality predicted higher PTG. Patients' spirituality should be part of intervention with breast cancer patients since it seems to be related to greater growth and adjustment to the illness.
Assuntos
Adaptação Psicológica , Neoplasias da Mama/psicologia , Crescimento Psicológico Pós-Traumático , Espiritualidade , Estresse Psicológico/psicologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Portugal , Religião e PsicologiaRESUMO
INTRODUCTION: Haemophilia is a bleeding disorder associated with significant pain, emotional distress, quality of life (QoL) impairment and considerable healthcare costs. Psychosocial health and effective pain management are considered essential end points for optimal haemophilia care, but there is a significant gap in evidence-based treatments targeting these outcomes in people with haemophilia (PWH). Psychological interventions are cost-effective in promoting emotional well-being, QoL and pain control, although these have been scarcely used in haemophilia field. This investigation aims to evaluate the effectiveness of two psychological interventions for pain management, emotional regulation and promotion of QoL in PWH. METHODS AND ANALYSIS: This is a single-centre parallel randomised controlled trial conducted at a European Haemophilia Comprehensive Care Centre in Portugal, with five assessment points: baseline (T0), postintervention (T1), 3 (T2), 6 (T3) and 12 (T4) months follow-up. Eligible adult males, with moderate or severe haemophilia A or B will be randomised to experimental (EG) or control (CG) group. Intervention is either cognitive-behavioural therapy (EG1) or hypnosis (EG2), both consisting of four weekly sessions following standardised scripts delivered by trained psychologists. Randomisation will be computer generated, allocation concealment will be guaranteed and outcome assessors will be blind to EG/CG allocation. Main outcomes are pain and haemophilia-related QoL and secondary outcomes include clinical (clotting factor replacement consumption, joint bleeding episodes, analgesic intake) and psychological (pain coping strategies, anxiety, depression, illness perceptions) variables, functional assessment of the joints, inflammatory biomarkers (cytokines, high-sensitivity C reactive protein) and white blood cell count. ETHICS AND DISSEMINATION: This study was approved by the competent authorities and all procedures will comply with international ethical guidelines for clinical studies involving humans. Written informed consent will be obtained from all participants. The dissemination plan includes peer-reviewed scientific publications, conference participation and web and media coverage. TRIAL REGISTRATION NUMBER: NCT02870452.
Assuntos
Terapia Cognitivo-Comportamental , Hemofilia A/psicologia , Hipnose , Manejo da Dor/métodos , Qualidade de Vida , Adaptação Psicológica , Adulto , Ansiedade/terapia , Análise Custo-Benefício , Depressão/terapia , Hemofilia A/terapia , Humanos , Masculino , Saúde Mental , Portugal , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Projetos de PesquisaRESUMO
This study focused on cognitive representations of low back pain patients receiving chiropractic ( n = 213) versus physiotherapy treatment ( n = 125). Variables assessed included satisfaction with care, illness perceptions, beliefs about pain and medicines, attitudes towards doctors and medicine, suffering, adherence and functional incapacity. In the chiropractic treatment, functional incapacity was predicted by painful symptoms, suffering and personal control, and in the physiotherapy treatment by age, pain intensity, positive suffering, care satisfaction, illness identity and medication adherence. The groups differed on all cognitive variables assessed. Interventions should take into consideration cognitive dimensions, across treatment modalities.
Assuntos
Terapia por Exercício/métodos , Conhecimentos, Atitudes e Prática em Saúde , Dor Lombar/psicologia , Dor Lombar/terapia , Manipulação Quiroprática/métodos , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients. STUDY DESIGN: Double blind, placebo-controlled. SETTING & PARTICIPANTS: Hemodialysis units and pediatric subjects receiving hemodialysis. INTERVENTION: After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)). OUTCOMES & MEASUREMENTS: Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product. RESULTS: 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group. LIMITATIONS: Low power to detect differences in safety between groups and a short-term study. CONCLUSION: Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.