Longitudinal changes in acylated versus unacylated ghrelin levels may be involved in the underlying mechanisms of the switch in nutritional phases in Prader-Willi syndrome

Introduction: Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. An elevated, more unfavorable ratio between acylated and unacylated ghrelin (AG/UAG ratio) might play a role in the underlying mechanisms of this switch. We aimed to assess the evolution of the appetite-regulating hormones acylated ghrelin (AG) and unacylated ghrelin (UAG) and the AG/UAG ratio and their association with the change in eating behavior in children with PWS, compared to healthy age-matched controls. Methods: A longitudinal study was conducted in 134 children with PWS and 157 healthy controls, from the Netherlands, France, and Belgium. Levels of AG and UAG and the AG/UAG ratio were measured and nutritional phases as reported for PWS were scored. Results: The AG/UAG ratio was lower in the first years of life in PWS than in controls and started to increase from the age of 3 years, resulting in a high-normal AG/UAG ratio compared to controls. The AG levels remained stable during the different nutritional phases (p = 0.114), while the UAG levels decreased from 290 pg/mL in phase 1a to 137 pg/mL in phase 2b (p < 0.001). The AG/UAG ratio increased significantly from 0.81 in phase 2a to 1.24 in phase 2b (p = 0.012). Conclusions: The change from failure to thrive to excessive weight gain and hyperphagia in infants and children with PWS coincides with an increase in AG/UAG ratio. The increase in AG/UAG ratio occurred during phase 2a, thus before the onset of hyperphagia

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care

<p>Abstract</p> <p>Background</p> <p>Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients cared for in primary care.</p> <p>Methods</p> <p>Forty four general practitioners recruited end-of-life cancer patients with an estimated life expectancy of half a year or shorter. The inclusion period was three years, follow-up lasted one additional year. Practices were monitored bimonthly to identify new cases. Unbearable aspects in five domains and overall unbearable suffering were quantitatively assessed (5-point scale) through patient interviews every two months with a comprehensive instrument. Scores of 4 (serious) or 5 (hardly can be worse) were defined unbearable. The last interviews before death were analyzed. Sources providing strength to bear suffering were identified through additional open-ended questions.</p> <p>Results</p> <p>Seventy six out of 148 patients (51%) requested to participate consented; the attrition rate was 8%, while 8% were alive at the end of follow-up. Sixty four patients were followed up until death; in 60 patients interviews were complete. Overall unbearable suffering occurred in 28%. A mean of 18 unbearable aspects was present in patients with serious (score 4) overall unbearable suffering. Overall, half of the unbearable aspects involved the domain of traditional medical symptoms. The most frequent unbearable aspects were weakness, general discomfort, tiredness, pain, loss of appetite and not sleeping well (25%-57%). The other half of the unbearable aspects involved the domains of function, personhood, environment, and nature and prognosis of disease. The most frequent unbearable aspects were impaired activities, feeling dependent, help needed with housekeeping, not being able to do important things, trouble accepting the situation, being bedridden and loss of control (27%-55%). The combination of love and support was the most frequent source (67%) providing strength to bear suffering.</p> <p>Conclusions</p> <p>Overall unbearable suffering occurred in one in every four end-of-life cancer patients. Half of the unbearable aspects involved medical symptoms, the other half concerned psychological, social and existential dimensions. Physicians need to comprehensively assess suffering and provide psychosocial interventions alongside physical symptom management.</p

Longitudinal telomere length and body composition in healthy term-born infants during the first two years of life

ArticleAuthorsMetricsCommentsMedia CoverageAbstractIntroductionMaterials and methodsResultsDiscussionSupporting informationAcknowledgmentsReferencesReader Comments (0)FiguresAbstractObjectiveLeukocyte telomere length (LTL) is one of the markers of biological aging as shortening occurs over time. Shorter LTL has been associated with adiposity and a higher risk of cardiovascular diseases. The objective was to assess LTL and LTL shortening during the first 2 years of life in healthy, term-born infants and to associate LTL shortening with potential stressors and body composition.Study designIn 145 healthy, term-born infants (85 boys), we measured LTL in blood, expressed as telomere to single-gene copy ratio (T/S ratio), at 3 months and 2 years by quantitative PCR technique. Fat mass (FM) was assessed longitudinally by PEAPOD, DXA, and abdominal FM by ultrasound.ResultsLTL decreased by 8.5% from 3 months to 2 years (T/S ratio 4.10 vs 3.75, pConclusionWe present longitudinal LTL values and show that LTL shortens considerably (8.5%) during the first 2 years of life. LTL shortening during first 2 years of life was associated with FM%, FMI and visceral FM at age 2 years, suggesting that adverse adiposity programming in early life could contribute to more LTL shortening.</div