Maternale uniparentale disomie 14. In de differentiaaldiagnose bij Prader-Willi-syndroom

Maternal uniparental disomy 14 is a rare genetic disorder in which both chromosomes 14 are maternally inherited. The disorder is characterised by neonatal hypotonia and feeding difficulties, intrauterine or later growth retardation, truncal obesity and precocious puberty. During the neonatal period its clinical phenotype shows great similarities with that of Prader-Willi syndrome. We describe two patients with dysmaturity, neonatal hypotonia and feeding difficulties who initially showed clinical signs of Prader-Willi syndrome. However, molecular testing for this disorder was normal. Some years later, additional molecular testing confirmed the diagnosis of maternal uniparental disomy 14. Maternal uniparental disomy 14 shows many phenotypic similarities with Prader-Willi syndrome. In a hypotonic neonate, molecular testing for maternal uniparental disomy 14 should therefore be considered if Prader-Willi syndrome has been exclude

Does a better adherence to dietary guidelines reduce mortality risk and environmental impact in the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition?

Guidelines for a healthy diet aim to decrease the risk of chronic diseases. It is unclear as to what extent a healthy diet is also an environmentally friendly diet. In the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition, the diet was assessed with a 178-item FFQ of 40 011 participants aged 20–70 years between 1993 and 1997. The WHO’s Healthy Diet Indicator (HDI), the Dietary Approaches to Stop Hypertension (DASH) score and the Dutch Healthy Diet index 2015 (DHD15-index) were investigated in relation to greenhouse gas (GHG) emissions, land use and all-cause mortality risk. GHG emissions were associated with HDI scores (−3·7 % per sd increase (95 % CI −3·4, −4·0) for men and −1·9 % (95 % CI −0·4, −3·4) for women), with DASH scores in women only (1·1 % per sd increase, 95 % CI 0·9, 1·3) and with DHD15-index scores (−2·5 % per sd increase (95 % CI −2·2, −2·8) for men and −2·0 % (95 % CI −1·9, −2·2) for women). For all indices, higher scores were associated with less land use (ranging from −1·3 to −3·1 %). Mortality risk decreased with increasing scores for all indices. Per sd increase of the indices, hazard ratios for mortality ranged from 0·88 (95 % CI 0·82, 0·95) to 0·96 (95 % CI 0·92, 0·99). Our results showed that adhering to the WHO and Dutch dietary guidelines will lower the risk of all-cause mortality and moderately lower the environmental impact. The DASH diet was associated with lower mortality and land use, but because of high dairy product consumption in the Netherlands it was also associated with higher GHG emissions

Does a better adherence to dietary guidelines reduce mortality risk and environmental impact in the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition?

Guidelines for a healthy diet aim to decrease the risk of chronic diseases. It is unclear as to what extent a healthy diet is also an environmentally friendly diet. In the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition, the diet was assessed with a 178-item FFQ of 40 011 participants aged 20–70 years between 1993 and 1997. The WHO’s Healthy Diet Indicator (HDI), the Dietary Approaches to Stop Hypertension (DASH) score and the Dutch Healthy Diet index 2015 (DHD15-index) were investigated in relation to greenhouse gas (GHG) emissions, land use and all-cause mortality risk. GHG emissions were associated with HDI scores (−3·7 % per sd increase (95 % CI −3·4, −4·0) for men and −1·9 % (95 % CI −0·4, −3·4) for women), with DASH scores in women only (1·1 % per sd increase, 95 % CI 0·9, 1·3) and with DHD15-index scores (−2·5 % per sd increase (95 % CI −2·2, −2·8) for men and −2·0 % (95 % CI −1·9, −2·2) for women). For all indices, higher scores were associated with less land use (ranging from −1·3 to −3·1 %). Mortality risk decreased with increasing scores for all indices. Per sd increase of the indices, hazard ratios for mortality ranged from 0·88 (95 % CI 0·82, 0·95) to 0·96 (95 % CI 0·92, 0·99). Our results showed that adhering to the WHO and Dutch dietary guidelines will lower the risk of all-cause mortality and moderately lower the environmental impact. The DASH diet was associated with lower mortality and land use, but because of high dairy product consumption in the Netherlands it was also associated with higher GHG emissions

Age-Related Neuronal Degeneration: Complementary Roles of Nucleotide Excision Repair and Transcription-Coupled Repair in Preventing Neuropathology

Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER) and transcription-coupled repair (TCR), two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pigmentosum (XP) and Cockayne syndrome (CS). TCR-deficient Csa(-/-) and Csb(-/-) CS mice showed activated microglia cells surrounding oligodendrocytes in regions with myelinated axons throughout the nervous system. This white matter microglia activation was not observed in NER-deficient Xpa(-/-) and Xpc(-/-) XP mice, but also occurred in Xpd XPCS mice carrying a point mutation (G602D) in the Xpd gene that is associated with a combined XPCS disorder and causes a partial NER and TCR defect. The white matter abnormalities in TCR-deficient mice are compatible with focal dysmyelination in CS patients. Both TCR-deficient and NER-deficient mice showed no evidence for neuronal degeneration apart from p53 activation in sporadic (Csa(-/-), Csb(-/-)) or highly sporadic (Xpa(-/-), Xpc(-/-)) neurons and astrocytes. To examine to what extent overlap occurs between both repair systems, we generated TCR-deficient mice with selective inactivation of NER in postnatal neurons. These mice develop dramatic age-related cumulative neuronal loss indicating DNA damage substrate overlap and synergism between TCR and NER pathways in neurons, and they uncover the occurrence of spontaneous DNA injury that may trigger neuronal degeneration. We propose that, while Csa(-/-) and Csb(-/-) TCR-deficient mice represent powerful animal models to study the mechanisms underlying myelin abnormalities in CS, neuron-specific inactivation of NER in TCR-deficient mice represents a valuable model for the role of NER in neuronal maintenance and survival

Narrative recognition and identification: a qualitative pilot study into reading literary texts with advanced cancer patients

Purpose: Patients with advanced cancer can experience their disease as a contingent life event. The sudden interruption of their life stories can obscure life goals and disrupt meaning making. In the context of the research project “In search of stories,” we aim to investigate the reading and discussion of selected stories which present ways of dealing with a contingent life event. In addition, we examine the use of a newly developed guide for reading these exemplary texts together with advanced cancer patients. Methods: This qualitative study describes the experiences of five patients with advanced cancer who participated in a guided reading and discussion about selected literary texts. The intervention consisted of reading a selected story, after which each patient was interviewed, using the reading guide as a conversation template. The interviews were then thematically analyzed for their conceptual content using a template analysis. Results: All five conversations showed some form of recognition in reaction to the chosen text, which led to personal identification of experiences of contingency, such as loss of life goals, impending death, or feelings of uncertainty. Besides the important role of identification, revealed by the responses to the questions in the reading guide, the discussion of the text helped them articulate their own experience and sources of meaning. Diverse worldviews came to the fore and concepts of meaning such as fate, life goals, quality of life, and death. Conclusions: First experiences with our newly developed reading guide designed to support a structured reading of stories containing experiences of contingency suggest that it may help patients to express their own experiences of contingency and to reflect on these experiences. Implications for Cancer Survivors: The intervention tested in this study may contribute to supportive care for survivors with advanced cancer, but further research is needed to evaluate its effect on quality of life