Eiberg H, Hansen L, Korbo L, Nielsen IM, Svenstrup K, Bech S, Pinborg LH, Friberg L, Hjermind LE, Olsen OR, Nielsen JE. Novel mutation in ATP13A2 widens the spectrum of Kufor‐Rakeb syndrome (PARK9).
...Kufor‐Rakeb syndrome (KRS) is a rare autosomal recessive inherited juvenile parkinsonian syndrome caused by mutations in ATP13A2. We describe six patients from a consanguineous Greenlandic Inuit family, homozygous for a novel frame‐shift mutation in exon 22 of ATP13A2 (c.2473C>AA, p.Leu825AsnfsX32). Disease onset varied from 10 to 29 years of age, the latest reported, and the clinical features were highly variable within a wide spectrum of an extrapyramidal–pyramidal syndrome with cognitive/psychiatric features. Ataxia was seen in two patients and axonal neuropathy in one, features not previously related to KRS. Dopamine transporter scans showed symmetrical, severely reduced uptake in striatum in two patients. Magnetic resonance imaging was without atrophy in one patient despite disease duration of 17 years, and cerebral and cerebellar atrophy was seen in another patient after 4 years of disease duration. The molecular pathogenic mechanisms of ATP13A2 mutations are discussed. The observation that the mutant transcript is not degraded by nonsense‐mediated RNA decay and the fact that none of the eight heterozygous carriers from the family have KRS symptoms suggest that the mutant protein does not interfere and destroy the function of the wild‐type ATP13A2 protein.
Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the ...Gemini Planet Imager, we discovered a planet orbiting the ∼20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 × 10–6 and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter.
A matter of size: The particle size effect on the activity of the oxygen reduction reaction of size‐selected platinum clusters was studied. The ORR activity decreased with decreasing Pt nanoparticle ...size, corresponding to a decrease in the fraction of terraces on the surfaces of the Pt nanoparticles (jk=kinetic current density, see picture).
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis ...(FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.
Porcine circovirus type 2 (PCV2) is the primary cause of Postweaning Multisystemic Wasting Syndrome (PMWS) in pigs. PCV2, however, is found in both PMWS-affected herds and non-affected herds. The ...objective of this study was to clarify if PCV2 genome nucleotide sequences isolated from pigs from PMWS-affected herds and non-affected herds cluster phylogenetically in two separate groups. All isolates (45) belonged to PCV2 group 1 and shared a nucleotide sequence identity of 99.4–100% indicating a very homogeneous PCV2 population in Denmark. Phylogenetic analysis of the PCV2 isolates revealed no distinctive clustering of case- and control-herds suggesting that there is no link between PCV2 sequences and herd disease status. The appearance of only PCV2 group 1 isolates in this study (isolates from 2003/2004) led us to determine if PCV2 nucleotide sequences had changed in Denmark over time. Interestingly, all PCV2 isolates from before the first outbreak of PMWS (2001) belonged either to a new PCV2 group identified for the first time in this study and named group 3 (isolates from 1980, 1987 and 1990) or PCV2 group 2 (isolates from 1993 and 1996). The shift from PCV2 group 2 to 1 was confirmed on a more global scale by placing all full genome PCV2 sequences submitted to GenBank from 1997 to 2006 in either of the groups by phylogenetic analysis. The analysis showed that the shift happened in 2003 or even earlier. This may indicate that PCV2 group 1 is a more adapted form of PCV2 and possibly could be more pathogenic.
Gestational weight gain (GWG) is associated with childhood obesity. We analyzed whether this effect persists into adulthood and is mediated by effects in childhood.
The design of the study a ...prospective birth cohort study established in 1959-1961.
The subjects were offspring (n = 4234 of whom 2485 had information from the last follow-up) of mothers included in 'The Copenhagen Perinatal Cohort' during pregnancy or at birth.
Information on maternal pre-pregnancy body mass index (BMI), GWG and several potential confounders were collected around delivery. Information on offspring BMI was available from various follow-up examinations from 1 to 42 years of age. The association of GWG with offspring BMI was analyzed by regression models including confounders. Using path analysis, the association of GWG with adult BMI was disentangled into an association mediated through childhood BMI and one independent hereof.
GWG was associated with offspring BMI at all ages. At the age of 42 years (n = 1540), there was an increasing risk of obesity (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.03-1.14 per kg GWG, P = 0.003). Only half of the association of GWG on offspring adult BMI was mediated through birth weight and BMI up to 14 years of age.
Greater GWG is associated with an increased BMI in childhood through adulthood and with an increased risk of obesity in adults. Only part of the association with adult BMI is mediated by childhood BMI, suggesting that excessive GWG induces a persisting susceptibility to obesogenic environments. As GWG is greater in women with small pre-pregnancy body weight, this implies a reinforcement of the obesity epidemic in the next generation. Our findings provide support for avoiding excessive GWG.
The objective of this study was to determine if increasing the energy and protein intake of heifer calves would affect growth rates, age at puberty, age at calving, and first lactation milk yield. A ...second objective was to perform an economic analysis of this feeding program using feed costs, number of nonproductive days, and milk yield data. Holstein heifer calves born at the Michigan State Dairy Cattle Teaching and Research Center were randomly assigned to 1 of 2 dietary treatments (n=40/treatment) that continued from 2 d of age until weaning at 42 d of age. The conventional diet consisted of a standard milk replacer 21.5% crude protein (CP), 21.5% fat fed at 1.2% of body weight (BW) on a dry matter basis and starter grain (19.9% CP) to attain 0.45kg of daily gain. The intensive diet consisted of a high-protein milk replacer (30.6% CP, 16.1% fat) fed at 2.1% of BW on a dry matter basis and starter grain (24.3% CP) to achieve 0.68kg of daily gain. Calves were gradually weaned from milk replacer by decreasing the amount offered for 5 and 12 d before weaning for the conventional and intensive diets, respectively. All calves were completely weaned at 42 d of age and kept in hutches to monitor individual starter consumption in the early postweaning period. Starting from 8 wk of age, heifers on both treatments were fed and managed similarly for the duration of the study. Body weight and skeletal measurements were taken weekly until 8 wk of age, and once every 4 wk thereafter until calving. Calves consuming the intensive diet were heavier, taller, and wider at weaning. The difference in withers height and hip width was carried over into the early post-weaning period, but a BW difference was no longer evident by 12 wk of age. Calves fed the intensive diet were younger and lighter at the onset of puberty. Heifers fed the high-energy and protein diet were 15 d younger at conception and 14 d younger at calving than heifers fed the conventional diet. Body weight after calving, daily gain during gestation, withers height at calving, body condition score at calving, calving difficulty score, and calf BW were not different. Energy-corrected, age-uncorrected 305-d milk yield was not different, averaging 9,778kg and 10,069kg for heifers fed the conventional and intensive diets, respectively. However, removing genetic variation in milk using parent average values as a covariate resulted in a tendency for greater milk from heifers fed the intensive diet. Preweaning costs were higher for heifers fed the intensive diet. However, total costs measured through first lactation were not different. Intensified feeding of calves can be used to decrease age at first calving without negatively affecting milk yield or economics.
To map COVID-19-specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID-19 pandemic in Denmark, and to explore characteristics of people with ...diabetes and high levels of worries related to the COVID-19 pandemic.
A cross-sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID-19-specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes-specific social support, diabetes distress and changes in diabetes-specific behaviours. Responses were analysed with descriptive statistics and logistic regressions.
People with diabetes have COVID-19-specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID-19, about one-third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID-19 and diabetes.
People with diabetes have COVID-19-specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID-19 and diabetes.
Transit through the carbon liquid phase has significant consequences for the subsequent formation of solid nanocarbon detonation products. We report dynamic measurements of liquid carbon condensation ...and solidification into nano-onions over ∽200 ns by analysis of time-resolved, small-angle X-ray scattering data acquired during detonation of a hydrogen-free explosive, DNTF (3,4-bis(3-nitrofurazan-4-yl)furoxan). Further, thermochemical modeling predicts a direct liquid to solid graphite phase transition for DNTF products ~200 ns post-detonation. Solid detonation products were collected and characterized by high-resolution electron microscopy to confirm the abundance of carbon nano-onions with an average diameter of ∽10 nm, matching the dynamic measurements. We analyze other carbon-rich explosives by similar methods to systematically explore different regions of the carbon phase diagram traversed during detonation. Our results suggest a potential pathway to the efficient production of carbon nano-onions, while offering insight into the phase transformation kinetics of liquid carbon under extreme pressures and temperatures.
Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ ...significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.
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