Family Matters:Trauma and Quality of Life in Family Members of Individuals With Prader-Willi Syndrome

BACKGROUND: Prader-Willi syndrome (PWS) is a potentially life threatening, genetic developmental disorder that requires lifelong medical treatment and behavioral management. PWS has a major impact on the patient's social environment. In this study, we have explored traumatic life events and symptoms of posttraumatic stress disorder (PTSD) in family members of individuals with PWS. We have also assessed quality of life in relation to trauma manifestations. In addition, we have evaluated demographic characteristics such as living setting of PWS patients as well as PWS symptom severity. METHODS: Data of this observational study were obtained by means of the Life Events Checklist DMS-5, the Posttraumatic Stress Disorder Checklist DSM-5, the abbreviated World Health Organization Quality of Life questionnaire, the Lancashire Quality of Life Profile questionnaire, and a short demographic inventory. The study sample includes 98 adults aged 19 to 80 years (M = 49, SD = 15), who are relatives of 69 individuals with PWS aged 0 to 58 years (M = 19, SD = 13). Participants were recruited via the two Dutch patient associations PWS and the Dutch Digital Center of Expertise PWS. RESULTS: Life time prevalence of traumatic events (93%) was higher in family members of PWS patients (“PWS relatives”) than in the general Dutch population (81%). Of those who reported any traumatic event, almost half reported PWS-related events. The prevalence of probable PTSD was higher in PWS relatives (12.1%) than the general lifetime prevalence of PTSD (worldwide, and in the Netherlands 7.4%). Predominant trauma symptoms in PWS relatives were “negative changes in arousal and reactivity” and “negative changes in cognition and mood;” both significantly negatively related to quality of life. Symptom severity of PWS individuals, as well as the associated trauma symptom severity of their relatives increased with age of the PWS individual. The presence of trauma symptoms was less frequent among relatives of PWS individuals living in a care facility. CONCLUSIONS: Having a relative with PWS is associated with higher prevalence of traumatic experiences and greater vulnerability to PTSD. Raising awareness in health care professionals of trauma symptoms in PWS relatives may contribute to effective treatment of their psychosocial stress. In addition, timely interventions might prevent family members from developing psychopathology like PTSD

Holistic lipidomics of the human gut phenotype using validated ultra-high-performance liquid chromatography coupled to hybrid orbitrap mass spectrometry

As lipids are assigned a plethora of biological functions, it is evident that dysregulated lipid metabolism signifies a key element in many pathological conditions. With this rationale, this study presents a validated lipidomics platform to map the fecal lipidome, which integrates unique information' about host-gut microbiome interactions, gastrointestinal functionality, and dietary patterns. This particular method accomplished coverage across all eight lipid categories: fatty acyls, glycerolipids, phosphoglycerolipids, polyketides, prenols, saccharolipids, sphingolipids, and sterols. Generic extraction of freeze-dried feces was achieved by solid-liquid extraction using methanol and methyl tert-butyl ether. Extracted components were separated by liquid chromatography, whereby the selected ethylene-bridged hybrid phenyl ultra-high-performance liquid chromatography stationary phase allowed fast separation of both individual lipid species and categories. Detection was achieved by high-resolution full-scan Q-Exactive Orbitrap mass spectrometry and covered a broad m/z scan range (67-2300 Da). Method validation was performed in a targeted fashion to evaluate the analytical performance across all lipid categories, revealing excellent linearity (R-2 >= 0.9921), acceptable repeatability (coefficients of variance = 0.90) for 75.3% and acceptable repeatability (coefficients of variance <= 30%) for 84.5% of about 9000 endogenous fecal compounds. Eventually, the potential of fecal lipidomics was exemplified within a clinical context of type 2 diabetes, thereby revealing significant perturbations [orthogonal partial least-squares discriminant analysis Q(2)(Y) of 0.728] in the fecal lipidome between participants with normal blood glucose levels (n = 26) and those with type 2 diabetes (n = 17)

Projectplan basistraining EML

Dit (deel-)project is gericht op het ontwikkelen van een hands-on basistraining EML 1.0. Deze training beoogt cursisten: * te leren werken met EML in concrete auteursomgeving (in casu Framemaker) * de uitgangspunten en grondbeginselen (technisch en onderwijskundig) van XML/EML te verduidelijken * inzicht te geven in de relatie tussen EML en XML * Inzicht te geven in de opzet van EML Aan het einde van de training is men in staat: * in Framemaker een EML-bestand (UOS met hoofdelementen) op te bouwen * de uitgangspunten en opbouw van EML te formuleren De training zal worden ontwikkeld in EML-versie 0.53 en worden uitgeleverd via het ELO-systeem

Адаптація в українській термінології іншомовних лексем на позначення засобів розміщення туристів

Розглянуто шляхи та причини запозичення іншомовної лексики на позначення засобів розміщення туристів, подано значення окремих запозичених лексем.The article studies the ways and reasons for lexical units denoting tourist accommodation borrowing. The meanings of some borrowed terms are given

Hypertension with hidden causes:the cognitive and behavioral profile of an adult female with chronic stress and 16p11.2 microdeletion

This case report aims to alert physicians to neuropsychological features and chromosomal variants that may underly resistant hypertension. We present a 35-year-old female patient with hypertensive crisis (BP 260/160 mmHg), initially treated with a combination of calcium antagonists, beta blockers, diuretics and angiotensin-converting enzyme (ACE)-inhibitors, though with little improvement. Cushing's syndrome, Conn's syndrome, and glucocorticoid receptor deficiency were ruled out. Multidisciplinary examination of medical history and (hetero)anamneses including psychosocial factors revealed mild dysmorphic body features, developmental delay, early diagnosis of autism spectrum disorder, a history of being bullied at school, little peer contact, learning disabilities, and special education. Neuropsychological assessment demonstrated below average to low average intelligence quotient, cognitive impairments, and psychopathology. Parallel genetic analyses revealed a rare 16p11.2 microdeletion syndrome. These concurrent examinations explained the patient's life-long high stress levels. After psychological treatment, with additional support at home, her blood pressure lowered to normal levels and antihypertensive drugs were no longer needed.</p

Coffee consumption is associated with a reduced risk of colorectal cancer recurrence and all-cause mortality

Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I–III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self-reported using questionnaires at the time of diagnosis. We retrieved recurrence and all-cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2-year median follow-up and 309 deaths during a 6.6-year median follow-up. Consuming more than 4 cups/d of coffee compared to an intake of &lt;2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all-cause mortality was U-shaped; coffee intake seemed optimal at 3–5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all-cause mortality. The association between coffee consumption and all-cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.</p

Coffee consumption is associated with a reduced risk of colorectal cancer recurrence and all-cause mortality

Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I–III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self-reported using questionnaires at the time of diagnosis. We retrieved recurrence and all-cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2-year median follow-up and 309 deaths during a 6.6-year median follow-up. Consuming more than 4 cups/d of coffee compared to an intake of &lt;2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all-cause mortality was U-shaped; coffee intake seemed optimal at 3–5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all-cause mortality. The association between coffee consumption and all-cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.</p

Publisher Correction: Lower body mass index and mortality in older adults starting dialysis (vol 8, 12858, 2018)

Clinical epidemiolog

Lower body mass index and mortality in older adults starting dialysis

Lower body mass index (BMI) has consistently been associated with mortality in elderly in the general and chronic disease populations. Remarkably, in older incident dialysis patients no association of BMI with mortality was found. We performed an in-depth analysis and explored possible time-stratified effects of BMI. 908 incident dialysis patients aged >= 65 years of the NECOSAD study were included, and divided into tertiles by baseline BMI (<23.1 ( lower), 23.1-26.0 ( reference), >= 26.0 (higher) kg/ m(2)). Because the hazards changed significantly during follow-up, the effect of BMI was modeled for the short-term (<1 year) and longer-term (>= 1 year after dialysis initiation). During follow-up (median 3.8 years) 567 deaths occurred. Lower BMI was associated with higher short-term mortality risk (adjusted-HR 1.63 [1.14-2.32] P = 0.007), and lower longer-term mortality risk (adjusted-HR 0.81 [0.63- 1.04] P = 0.1). Patients with lower BMI who died during the first year had significantly more comorbidity, and worse self-reported physical functioning compared with those who survived the first year. Thus, lower BMI is associated with increased 1-year mortality, but conditional on surviving the first year, lower BMI yielded a similar or lower mortality risk compared with the reference. Those patients with lower BMI, who had limited comorbidity and better physical functioning, had better survival

Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness