Lower Intake of Saturated Fatty Acids Is Associated with Improved Lipid Profile in a 6-Year-Old Nationally Representative Population

To strengthen the organization of new national dietary surveys and interventions in childhood, our aim was to study macronutrient intake and blood lipid profile at 6 years of age by comparing results from two earlier population-based cohorts. Subjects were n = 131 and n = 162 in the years 2001–2002 and 2011–2012, respectively. Three-day weighed food records were used to estimate diet and calculate nutrient intake. Total cholesterol, HDL-cholesterol and triacylglycerol were measured in serum and LDL-cholesterol was calculated. The average intake of saturated fatty acids (SFA) and trans FA was lower in 2011–2012 than 2001–2002 (13.3E% vs. 14.7E%, p < 0.001, and 0.8E% vs. 1.4E%, p < 0.001, respectively), replaced by a higher intake of unsaturated fatty acids. Total cholesterol and LDL-cholesterol were significantly lower in 2011–2012 than 2001–2002 (4.6 vs. 4.4 mmol/L, p = 0.003 and 2.8 vs. 2.5 mmol/L, p < 0.001, respectively). In a multiple linear regression model, one E% increase in SFA intake was related to a 0.03 mmol/L increase in LDL cholesterol (p = 0.04). A lower intake of saturated and trans fatty acids, replaced by unsaturated fatty acids, may have contributed to an improved lipid profile in a healthy 6-year-old population. Biological data for analysis of blood lipids are important in national dietary surveys in healthy children to monitor important health outcomes of interventions.     

Iodine status of breastfed infants and their mothers' breast milk iodine concentration

Iodine is an essential nutrient for growth and development during infancy. Data on iodine status of exclusively (EBF) and partially breastfed (PBF) infants as well as breast milk iodine concentration (BMIC) are scarce. We aimed to assess (a) infant iodine nutrition at the age of 5.5 months by measuring urinary iodine concentration (UIC) in EBF (n = 32) and PBF (n = 28) infants and (b) mothers' breast milk iodine concentration (n = 57). Sixty mother–infant pairs from three primary health care centres in Reykjavik and vicinities provided urine and breast milk samples for iodine analysis and information on mothers' habitual diet. The mother–infant pairs were participants of the IceAge2 study, which focuses on factors contributing to infant growth and development, including body composition and breast‐milk energy content. The median (25th–75th percentiles) UIC was 152 (79–239) μg/L, with no significant difference between EBF and PBF infants. The estimated median iodine intake ranged from 52 to 86 μg/day, based on urinary data (assuming an average urine volume of 300–500 ml/day and UIC from the present study). The median (25th–75th percentiles) BMIC was 84 (48–114) μg/L. It is difficult to conclude whether iodine status is adequate in the present study, as no ranges for median UIC reflecting optimal iodine nutrition exist for infants. However, the results add important information to the relatively sparse literature on UIC, BMIC, and iodine intake of breastfed infants.     

GDF15 promotes simultaneous astrocyte remodeling and tight junction strengthening at the blood–brain barrier

Perivascular astrocyte processes (PAP) surround cerebral endothelial cells (ECs) and modulate the strengthening of tight junctions to influence blood–brain barrier (BBB) permeability. Morphologically altered astrocytes may affect barrier properties and trigger the onset of brain pathologies. However, astrocyte-dependent mediators of these events remain poorly studied. Here, we show a pharmacologically driven elevated expression and release of growth/differentiation factor 15 (GDF15) in rat primary astrocytes and cerebral PAP. GDF15 has been shown to possess trophic properties for motor neurons, prompting us to hypothesize similar effects on astrocytes. Indeed, its increased expression and release occurred simultaneously to morphological changes of astrocytes in vitro and PAP, suggesting modulatory effects of GDF15 on these cells, but also neighboring EC. Administration of recombinant GDF15 was sufficient to promote astrocyte remodeling and enhance barrier properties between ECs in vitro, whereas its pharmacogenetic abrogation prevented these effects. We validated our findings in male high anxiety-related behavior rats, an animal model of depressive-like behavior, with shrunk PAP associated with reduced expression of the junctional protein claudin-5, which were both restored by a pharmacologically induced increase in GDF15 expression. Thus, we identified GDF15 as an astrocyte-derived trigger of astrocyte process remodeling linked to enhanced tight junction strengthening at the BBB.     

Tumor genetics and survival of thymic neuroendocrine neoplasms: A multi‐institutional clinicopathologic study

Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical carcinoids [TAC], and 20 high‐grade neuroendocrine carcinomas [HGNEC] of the thymus), contributed by multiple institutions. The mean number of chromosomal imbalances per tumor was 0.8 in TTC (31% aberrant cases) versus 1.1 in TAC (44% aberrant cases) versus 4.7 in HGNEC (75% aberrant cases). Gains of 8q24 (MYC gene locus) were the most frequent alteration and one of the overlapping features between carcinoids and HGNEC. The 5‐year survival rates for TTC, TAC, and HGNEC were 100, 60, and 30%. The 10‐year survival rates for TTC and TAC were 50 and 30% (P = 0.002). Predictive mitotic cut‐off values for TTC versus TAC were 2.5 per 10 high‐power fields (HPF; indicating a higher death rate, P = 0.062) and 15 per 10 HPF (indicating higher risk of recurrence, P = 0.036) for separating HGNEC from TAC. We conclude that the current histopathologic classifications of TNET reflect tumor biology and provide important information for therapeutic management. © 2014 Wiley Periodicals, Inc.     

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.     

Spongiform encephalopathy in siblings with no evidence of protease-resistant prion protein or a mutation in the prion protein gene

We discuss relevant aspects in two siblings with a neurodegenerative process of unclear aetiology who developed progressive dementia with global aphasia and hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years after disease onset. The cases were reported to the National Reference Center for TSE Surveillance in Göttingen, Germany. Detailed clinical examinations, CSF, blood samples, and copies of the important diagnostic tests (magnetic resonance imaging, electroencephalogram, laboratory tests) were obtained. Further neuropathological and genetic analyses were performed. Cerebral magnetic resonance imaging of both siblings showed prominent changes in signal intensity, especially in the left medial temporal cortex, but also the hippocampal formation. Neuropathological examination revealed spongiform changes, neuronal loss, and astrocytic gliosis, which are typical in Creutzfeldt–Jakob disease. However, no prion protein deposits were detectable by immunohistochemical analysis, Western blot, or PET blot, though abundant tau protein deposits were observed. A mutation in the coding region of the prion protein genes of both siblings was excluded. A detailed search of the literature revealed no other cases with a similar clinical and neuropathological appearance. While the disease aetiology remains unclear, the findings point to a neurodegenerative process and most likely a genetic disease.