Appetite stimulation with cannabis-based medicine and methods for assessment of glomerular filtration in older patients with medical illness: A study protocol.

BACKGROUND AND AIM: Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. METHODS AND OBJECTIVES: This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

Danish milk consumers are critical of advanced breeding methods in dairy production, but only 1 in 5 is unwilling to drink milk from dairy cows bred with semen derived from such methods.

Assisted reproductive technologies and genetic technologies can accelerate progress in breeding programs in dairy farming, but it is unclear how consumers will react to the use of these technologies. Using representative questionnaire data on Danish citizens (n = 2,036) this cross-sectional study examined consumer attitudes to the application of advanced technologies in dairy cattle breeding. Attitudes were examined in 2 ways. First, we prompted about general attitudes to assisted reproductive technologies and genetic technologies in dairy cow breeding. Here we found that most of the participants were critical of cow impregnation involving hormone therapy and the insertion of cloned fetuses. Second, we used a vignette experiment to study whether acceptance of and willingness to drink milk varies with the type of technique that farmers use for their breeding work, as well as the traits being bred for. We included 5 breeding methods with differing degrees of technological complexity. Participants were randomly assigned to receive tailored information about 1 of the 5 breeding methods. The information specified that dairy farmers' own use of advanced technologies is limited to using semen in artificial insemination on the farm. The potentially concerning technologies are here not applied at farm level but are represented in the semen used in artificial insemination because they were used by breeders on earlier generations of cows and bulls to develop semen with higher genetic merit. There was much less concern about this indirect use of the technologies. Only 1 in 5 participants thought the most advanced method we prompted about (use of semen from breeding methods involving genetic engineering and cloning) was unacceptable. Unwillingness to drink milk from cows produced through such a breeding method was also modest (18%) and not much higher than the unwillingness to drink milk from a cow produced by natural fertilization (10%). A likely reason for the unexpectedly low level of unwillingness to drink milk is that people regard the genetic engineering as distant from the final product. We also found that high-frequency organic milk consumers were more critical of advanced breeding methods. Thus, 28% within this group were unwilling to drink milk from cows impregnated with semen derived from earlier generations of cows and bulls bred using gene editing and cloning. Further, this share rose if the high-frequency organic consumers were very averse to the manipulation of nature. The organic sector may need to cater to this subgroup (e.g., by ensuring the traceability of the semen that organic farmers use to artificially inseminate their cows).

Dilated Optic Nerve Sheath in Mucopolysaccharidosis I: Common and Not Necessarily High Intracranial Pressure.

Hydrocephalus is one of the earliest manifestations of mucopolysaccharidosis I-Hurler syndrome, and delayed treatment of hydrocephalus can lead to neurocognitive delay or even death. Optic nerve sheath diameter has been established as a noninvasive measurement to detect elevated intracranial pressure. This study aimed to establish correlations between optic nerve sheath diameter and opening pressure. Forty-nine MR images and opening pressures in patients with mucopolysaccharidosis I-Hurler syndrome were retrospectively reviewed from 2008 to 2020. The optic nerve sheath diameter was measured 3 mm posterior to the posterior margin of the globe (retrobulbar) and 10 mm anterior to the optic foramen (midpoint segment), and the average was taken between the 2 eyes. Opening pressure was measured with the patient in the lateral decubitus position with controlled end-tidal CO2 on the same day as the MR imaging. The average retrobulbar optic nerve sheath diameter was 5.33 mm, higher than the previously reported measurement in healthy controls, in patients with idiopathic intracranial hypertension, and there was a positive correlation between age and the optic nerve sheath diameter measured at the retrobulbar or midpoint segment (retrobulbar segment, R 2 = 0.27, P < .01; midpoint segment, R 2 = 0.20, P < .01). However, there was no correlation between retrobulbar or midpoint segment optic nerve sheath diameter and opening pressure (retrobulbar segment, R 2 = 0.02, P = .17; midpoint segment, R 2 = 0.03, P < .12). This study shows a higher average optic nerve sheath diameter in patients with mucopolysaccharidosis I-Hurler syndrome than in healthy controls regardless of the location of the measurement. However, the degree of optic nerve sheath dilation does not correlate with opening pressure, suggesting that increased optic nerve sheath diameter is an ocular manifestation of mucopolysaccharidosis I-Hurler syndrome itself rather than a marker of elevated intracranial pressure.

Danish dairy farmers' acceptance of and willingness to use semen from bulls produced by means of in vitro embryo production and genomic selection.

A novel technology combining in vitro production and genomic embryo selection is currently under development in dairy cattle breeding. Adoption of this technology will probably accelerate genetic progress toward the main breeding goals of economic interest, as well as allow selection for traits of societal concern such as decreased methane emissions and improved animal welfare. However, dairy farmers, and especially organic farmers, could find the technology morally questionable and reject its use. This cross-sectional study surveyed Danish dairy farmers' general acceptance of the combined technology and their reported likelihood of using semen produced with it. Drawing on diffusion theory, a questionnaire was developed to examine the way farmers discover and communicate about new technological breeding options, and to measure the factors which predict acceptance and likelihood of adopting the technology. The questionnaire was sent to a randomly selected sample of organic and conventional dairy farmers in Denmark, and 85 organic and 71 conventional farmers (41% response rate) completed it. Seventy-six percent of farmers reported that they would be likely to use semen from bulls derived from the technology. A majority (61%) also found the technology acceptable, but many (33%) were unsure or undecided. Most farmers saw the technology as beneficial, but ethical reservations were aired by around a fifth of the farmers. There were no differences between organic and conventional farmers in likelihood of using, perceived utility, and ethical reservations about the technology. Self-reported idealistic organic farmers showed lower acceptance of the technology, but reported similar likelihood of using semen produced by it. Young farmers (20-39 yr) exhibited higher acceptance of the technology. Larger producers (in terms of number of cows) were more likely to report that they will use and accept the technology. We conclude that it is likely that semen from the technology combining in vitro production and genomic selection would be widely used by both organic and conventional farmers provided that costs can be kept low, and that there are advantages in terms of achieving breeding goals. Structural developments, growth in size of dairy farms, acceptance by young farmers, and the fact that economic incentives (and even ethical arguments) seem to favor the technology all point to this conclusion.

Antimicrobial resistance and virulence characteristics in 3 collections of staphylococci from bovine milk samples.

Mastitis is a prevalent disease in dairy cattle, and staphylococci are among the most common causative pathogens. Staphylococci can express resistance to a range of antimicrobials, of which methicillin resistance is of particular public health concern. Additionally, Staphylococcus aureus carries a variety of virulence factors, although less is understood about the virulence of non-aureus staphylococci (NAS). The aim of our study was to identify and characterize 3 collections of staphylococcal isolates from bovine milk samples regarding antimicrobial resistance, with emphasis on methicillin resistance, and their carriage of virulence genes typically displayed by Staph. aureus. A total of 272 staphylococcal isolates collected in Norway and Belgium in 2016 were included, distributed as follows: group 1, Norway, 100 isolates; group 2, Flanders, Belgium, 64 isolates; group 3, Wallonia, Belgium, 108 isolates. Species identification was performed by use of MALDI-TOF mass spectrometry. Phenotypic resistance was determined via disk diffusion, and PCR was used for detection of methicillin resistance genes, mecA and mecC, and virulence genes. Antimicrobial resistance was common in Staphylococcus epidermidis and Staphylococcus haemolyticus from all different groups, with resistance to trimethoprim-sulfonamide frequently occurring in Staph. epidermidis and Staph. haemolyticus as well as in Staph. aureus. Resistance to penicillin was most frequently observed in group 1. Ten Belgian isolates (1 from group 2, 9 from group 3) carried the methicillin resistance determinant mecA: 5 Staph. aureus from 2 different farms and 5 NAS from 3 different farms. Almost all Staph. aureus isolates were positive for at least 3 of the screened virulence genes, whereas, in total, only 8 NAS isolates harbored any of the same genes. Our study contributes to the continuous need for knowledge regarding staphylococci from food-producing animals as a basis for better understanding of occurrence of resistance and virulence traits in these bacteria.

In vitro and in vivo assessment of phage therapy against Staphylococcus aureus causing bovine mastitis.

OBJECTIVE: The aim of this study was to assess the efficacy of lytic bacteriophages on Staphylococcus aureus causing bovine mastitis, by in vitro and in vivo assays using Galleria mellonella and murine mastitis models. METHODS: Between May and December 2016, ten S. aureus (five methicillin-resistant and five methicillin-sensitive) isolates were isolated from milk samples of cattle with mastitis in Belgium and Norway. The isolates were assessed in vitro for their susceptibility to four lytic bacteriophages (Romulus, Remus, ISP and DSM105264) and subsequently in vivo in G. mellonella larvae and in murine mastitis model. RESULTS: Romulus, Remus and ISP showed a lytic activity against the S. aureus isolates in vitro. A larvae survival rate below 50% was observed at 4 days post-inoculation (DPI) in the groups infected with a methicillin-sensitive S. aureus isolate and treated with these three phages in vivo. An incomplete recovery of the mouse mastitis was observed at 48h post-inoculation (HPI) in the groups infected and treated with the ISP phage in vivo. CONCLUSIONS: The observations are much more pronounced statistically between the infected- phosphate buffered saline (PBS)-treated and infected-phage-treated groups in G. mellonella and the murine mastitis model demonstrating an effect of the phages against S. aureus associated with bovine mastitis.

Neutering increases the risk of obesity in male dogs but not in bitches - A cross-sectional study of dog- and owner-related risk factors for obesity in Danish companion dogs.

Knowledge of risk factors for canine obesity is an important pre-requisite of effective preventative strategies. This study aimed to investigate risk factors for canine obesity in adult companion dogs across Zealand, Denmark. Client-owned dogs (>2 years of age and without chronic illness) were recruited and examined at eight companion animal veterinary practices in areas with varying socio-economic characteristics. The body condition score (BCS) of the dogs was examined by two investigators based on a 9-point scoring scheme. Dog owners answered a questionnaire that had prompts regarding: 1) dog characteristics, including neuter status, 2) owner characteristics, 3) feeding and exercise practices and 4) the owners' attachment to the dog. The effect of these factors on BCS and the risk of being heavy/obese (BCS scores 7-9) were analysed in two separate analyses. A total of 268 dogs were included in the analysis, of which 20.5% were found to be heavy/obese. The average BCS was 5.46. In terms of dog characteristics, neutering dramatically increased both BCS and the risk of being heavy/obese in male dogs but not in bitches. BCS and the risk of being heavy/obese increased in senior bitches and decreased in senior male dogs. The risk of being heavy/obese was higher in dogs with overweight and obese owners. Regarding feeding and exercise practices, providing only one meal per day increased BCS and risk of being heavy/obese. Treats during relaxation increased the risk of dogs being heavy/obese. It also increased the dogs' BCS, but only if the owners were overweight or obese. An increased duration of daily walking increased the risk of the dog being heavy/obese, but only if the owner was overweight or obese. Allowing the dog to run free in the garden/property decreased the risk of the dog being heavy/obese. The owners' attachment to the dog was not associated with the dogs' BCS or dogs' being heavy/obese. An important and novel finding was that neutering increased the risk of being overweight or obese for male dogs while bitches were at risk irrespective of neuter status. Furthermore, a complex interaction between owners' weight status, feeding practices and the risk of dogs being overweight or obese was found, which stresses the need to consider companion animal obesity from a One Health perspective in future prospective studies. Finally, this study was unable to confirm that canine obesity is a product of owners being too attached to their dogs.

Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine.

Human chorionic gonadotrophin (hCG) and its ß-subunit (hCGß) are tumour autocrine growth factors whose presence in the serum of cancer patients has been linked to poorer prognosis. Previous studies have shown that vaccines which target these molecules and/or the 37 amino acid C-terminal hCGß peptide (hCGßCTP) induce antibody responses in a majority of human recipients. Here we explored whether the immunogenicity of vaccines containing an hCGß mutant (hCGßR68E, designed to eliminate cross-reactivity with luteinizing hormone) or hCGßCTP could be enhanced by coupling the immunogen to different carriers [keyhole limpet haemocyanin (KLH) or heat shock protein 70 (Hsp70)] using different cross-linkers [1-ethyl-3(3-dimethylaminopropyl)carboiimide (EDC) or glutaraldehyde (GAD)] and formulated with different adjuvants (RIBI or Montanide ISA720). While there was little to choose between KLH and Hsp70 as carriers, their influence on the effectiveness of a vaccine containing the BAChCGßR68E mutant was less marked, presumably because, being a foreign species, this mutant protein itself might provide T helper epitopes. The mutant provided a significantly better vaccine than the hCGßCTP peptide irrespective of the carrier used, how it was cross-linked to the carrier or which adjuvant was used when hCG was the target. Nonetheless, for use in humans where hCG is a tolerated self-protein, the need for a carrier is of fundamental importance. Highest antibody titres were obtained by linking the BAChCGßR68E to Hsp70 as a carrier by GAD and using RIBI as the adjuvant, which also resulted in antibodies with significantly higher affinity than those elicited by hCGßCTP peptide vaccine. This makes this mutant vaccine a promising candidate for therapeutic studies in hCGß-positive cancer patients.

Safety evaluation of a novel muramidase for feed application.

Safety evaluation of a muramidase produced by a Trichoderma reesei strain (safe lineage), expressing a muramidase gene isolated from Acremonium alcalophilum is presented. Intended use in feed of this enzyme is as digestive aid in broiler chickens. Muramidase 007, was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 90-day subchronic toxicity studies in rats at doses up to 1132 mg TOS/kg body weight/day. The enzyme did not exhibit, in vitro, skin, nor eye irritation potential. Acute aquatic toxicity evaluated on daphnia and algae showed absence of effect of the enzyme at the standard doses tested. Muramidase 007 was fully tolerated by broiler chickens in a 6-weeks tolerance study showing no adverse effects in any of the dietary treatments (0, 1×, 5× and 10× maximum recommended dose). In conclusion, Muramidase 007 is found to be toxicologically inert, and there are no worker's safety concerns if standard precautions are instituted and a non-dusty formulation is employed. Muramidase 007 is well tolerated by the target species (broiler chickens) and cause no harm to the environment. The beneficial safety evaluation of Muramidase 007 is in line with this type of enzyme that is found ubiquitously in nature.

Eating out in four Nordic countries: National patterns and social stratification.

Using a survey conducted in four Nordic countries (Denmark, Finland, Norway and Sweden) in 2012, we investigated whether eating out in cafés and restaurants in these countries is best characterized as a workday pattern activity or a leisure activity; and, whether frequent eating at cafés and restaurants is related to socio-demographic factors and factors relevant to the organization of daily life. We found that eating out is not a fundamental part of everyday eating. It is something which takes place occasionally. This may be taken to suggest that eating out in the Nordic countries is primarily a leisure activity. However, while this is an accurate portrayal of Denmark and Norway, eating out in Finland and Sweden is somewhat more common and linked to work-life. This difference probably reflects contrasting historical-institutional paths: in Finland and Sweden a food culture emphasizing cooked lunches and dedicated public policies supporting the provisioning of lunches outside the home may have promoted eating out. Multivariate analysis revealed that eating out declines with age. An urbanization effect exists, as residence in a capital city increases the propensity to eat out. There were socio-economic differences in all countries. We hypothesized that education and status would not significantly explain eating out activity after people's gastronomic interest had been controlled for. However, education was statistically significant in Sweden and Norway, and surprisingly status was negatively associated with eating out in Sweden. As expected, eating out was positively associated with income, and it was more frequent among the higher salariat and the self-employed (although not in Norway).

Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome.

Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. We examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children's Hospital or the University of Minnesota Children's Hospital from 1983 to 2016. Implementation of busulfan pharmacokinetic monitoring started in 2004 in both institutions. Two hundred and forty HS children were included in this analysis (historical era (pre-2004), n=131; current era (post 2004), n=109). The proportion of patients with graft failure was significantly lower in the current era compared with the historical era (37.2% vs 10.1%, respectively). Of 49 patients with graft failure in the historical era, 1 had aplasia and 48 had autologous reconstitution. All the 11 graft failures of the current era occurred in recipients of cord blood transplants (7 aplasia and 4 autologous reconstitution). The outcomes of second transplant in these patients has improved, with 89% of such patients alive and engrafted in the current era compared with 58% in the historical era. The pattern of graft failure has changed from autologous reconstitution, likely secondary to inadequate myelosuppression in the historical era, to aplasia in the current era, likely due to imperfect immunosuppression.

Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds.

A number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from a nationwide Danish dog registry and invited to participate. Of these, 911 responded, giving a final sample of 846. There were clear differences between owners of the four breeds with respect to degree of planning prior to purchase, with owners of Chihuahuas exhibiting less. Motivations behind choice of dog were also different. Health and other breed attributes were more important to owners of Cairn Terriers, whereas the dog's personality was reported to be more important for owners of French Bulldogs and Cavalier King Charles Spaniels but less important for Chihuahua owners. Higher levels of health and behavior problems were positively associated with a closer owner-dog relationship for owners of Cavalier King Charles Spaniels and Chihuahuas but, for owners of French Bulldogs, high levels of problems were negatively associated with an intention to procure the same breed again. In light of these findings, it appears less paradoxical that people continue to buy dogs with welfare problems.

Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature.

Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders such as selected lysosomal disorders, cerebral adrenoleukodystrophy and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated PBSCs. Median age at time of second HCT was 6.6 years (1.1-14.6 years). Fourteen of seventeen patients (82%) achieved engraftment, with a 3-year overall survival of 82% (95% CI, 54-94%). Day 100 transplant-related mortality was 12% (95% CI, 0-27%). CMV and adenovirus reactivation occurred in 30% and fungal infections in 18%. The incidence of grade II-IV acute GvHD disease was 35% (95% CI, 13-58%) with only 6% grade III-IV (95% CI, 0-17%). In summary, we illustrate excellent overall survival and acceptable toxicity using a non-myeloablative conditioning regimen for second HCT as salvage therapy for first GF in patients with non-malignant conditions.

Early neonatal lamb mortality: postmortem findings.

An investigation of stillbirth and early neonatal lamb mortality was conducted in sheep flocks in Norway. Knowledge of actual causes of death are important to aid the interpretation of results obtained during studies assessing the risk factors for lamb mortality, and when tailoring preventive measures at the flock, ewe and individual lamb level. This paper reports on the postmortem findings in 270 liveborn lambs that died during the first 5 days after birth. The lambs were from 17 flocks in six counties. A total of 27% died within 3 h after birth, 41% within 24 h and 80% within 2 days. Most lambs (62%) were from triplet or higher order litters. In 81% of twin and larger litters, only one lamb died. The most frequently identified cause of neonatal death was infectious disease (n=97, 36%); 48% (n=47) of these died from septicaemia, 25% (n=24) from pneumonia, 22% (n=21) from gastrointestinal infections and 5% (n=5) from other infections. Escherichia coli accounted for 65% of the septicaemic cases, and were the most common causal agent obtained from all cases of infection (41%). In total, 14% of neonatal deaths resulted from infection by this bacterium. Traumatic lesions were the primary cause of death in 20% (n=53) of the lambs. A total of 46% of these died within 3 h after birth and 66% within 24 h. Severe congenital malformations were found in 10% (n=27) of the lambs, whereas starvation with no concurrent lesions was the cause of death in 6% (n=17). In 16% (n=43) of the lambs, no specific cause of death was identified, lambs from triplet and higher order litters being overrepresented among these cases. In this study, the main causes of neonatal lamb mortality were infection and traumatic lesions. Most neonatal deaths occurred shortly after birth, suggesting that events related to lambing and the immediate post-lambing period are critical for lamb survival.

Veterinarian's dilemma: a study of how Danish small animal practitioners handle financially limited clients.

This study examined the extent to which Danish veterinary practices encounter financially limited clients and how different factors relating to the animal, the client and the veterinarian affect decisions to provide treatment for these clients. 300 small animal practices were invited to participate in an online survey. 195 participated, giving a response rate of 65 per cent. The results show that Danish small animal veterinary practices encounter clients with limited finances regularly: 33.8 per cent of them 3-4 times, 24.6 per cent 5-10 times and 19.5 per cent 1-2 times a month. Only around 9 per cent reported having a written practice policy on handling financially limited clients. Factors affecting decisions to treat include the severity and type of the animal's condition, the medical care needed and the client's expressed emotions. The propensity to treat is significantly higher in female veterinarians and in situations involving unborn animals. The overall conclusion is that small animal veterinary practices often provide treatment to clients who are not able to pay-far beyond what is legally required. This can be considered a major economic and psychological challenge for the practising veterinarians.

Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients.

BACKGROUND AND PURPOSE: Outcomes following hematopoietic stem cell transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MR imaging gadolinium intensity scoring system improves prediction of neurologic outcome. MATERIALS AND METHODS: We developed a 4-point scale of gadolinium intensity relative to the choroid plexus: 0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The interobserver concordance of the scale was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with CSF chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplantation. For 25 evaluable higher risk patients (Loes ≥10), the gadolinium intensity score was compared with longer term posttransplantation clinical change. RESULTS: The gadolinium intensity scoring system showed good interobserver reproducibility (κ = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant CSF chitotriosidase activity in nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and 3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense pretransplantation brain MR imaging gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplantation: 0/1: adrenoleukodystrophy neurologic function scale score difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale score difference = 10.4, n = 18 (P = .05). CONCLUSIONS: Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy. The enhancement score significantly correlates with chitotriosidase. In boys with higher risk cerebral disease (Loes ≥10), the enhancement score itself predicts neurologic outcome following treatment. Such data may help guide treatment decisions for clinicians and families.

Brains striving for coherence: Long-term cumulative plot formation in the default mode network.

Many everyday activities, such as engaging in conversation or listening to a story, require us to sustain attention over a prolonged period of time while integrating and synthesizing complex episodic content into a coherent mental model. Humans are remarkably capable of navigating and keeping track of all the parallel social activities of everyday life even when confronted with interruptions or changes in the environment. However, the underlying cognitive and neurocognitive mechanisms of such long-term integration and profiling of information remain a challenge to neuroscience. While brain activity is generally traceable within the short time frame of working memory (milliseconds to seconds), these integrative processes last for minutes, hours or even days. Here we report two experiments on story comprehension. Experiment I establishes a cognitive dissociation between our comprehension of plot and incidental facts in narratives: when episodic material allows for long-term integration in a coherent plot, we recall fewer factual details. However, when plot formation is challenged, we pay more attention to incidental facts. Experiment II investigates the neural underpinnings of plot formation. Results suggest a central role for the brain's default mode network related to comprehension of coherent narratives while incoherent episodes rather activate the frontoparietal control network. Moreover, an analysis of cortical activity as a function of the cumulative integration of narrative material into a coherent story reveals to linear modulations of right hemisphere posterior temporal and parietal regions. Together these findings point to key neural mechanisms involved in the fundamental human capacity for cumulative plot formation.

Mean Diffusional Kurtosis in Patients with Glioma: Initial Results with a Fast Imaging Method in a Clinical Setting.

BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an MR imaging technique that provides microstructural information in biologic systems. Its application in clinical studies, however, is hampered by long acquisition and postprocessing times. We evaluated a new and fast (2 minutes 46 seconds) diffusional kurtosis imaging method with regard to glioma grading, compared it with conventional diffusional kurtosis imaging, and compared the diagnostic accuracy of fast mean kurtosis (MK') to that of the widely used mean diffusivity. MATERIALS AND METHODS: MK' and mean diffusivity were measured in the contrast-enhancing tumor core, the perifocal hyperintensity (indicated on T2 FLAIR images), and the contralateral normal-appearing white and gray matter of 34 patients (22 with high-grade and 12 with low-grade gliomas). MK' and mean diffusivity in the different tumor grades were compared by using a Wilcoxon rank sum test. Receiver operating characteristic curves and the areas under the curve were calculated to determine the diagnostic accuracy of MK' and mean diffusivity. RESULTS: MK' in the tumor core, but not mean diffusivity, differentiated high-grade from low-grade gliomas, and MK' differentiated glioblastomas from the remaining gliomas with high accuracy (area under the curveMK' = 0.842; PMK' < .001). MK' and mean diffusivity identified glioblastomas in the group of high-grade gliomas with similar significance and accuracy (area under the curveMK' = 0.886; area under the curvemean diffusivity = 0.876; PMK' = .003; Pmean diffusivity = .004). The mean MK' in all tissue types was comparable to that obtained by conventional diffusional kurtosis imaging. CONCLUSIONS: The diffusional kurtosis imaging approach used here is considerably faster than conventional diffusional kurtosis imaging methods but yields comparable results. It can be accommodated in clinical protocols and enables exploration of the role of MK' as a biomarker in determining glioma subtypes or response evaluation.

Eating practices and diet quality: a population study of four Nordic countries.

BACKGROUND/OBJECTIVES: Daily practices related to eating are embedded in the social and cultural contexts of everyday life. How are such factors associated with diet quality relative to motivational factors? And, are associations universal or context-specific? We analyze the relationship between diet quality and the following practices: social company while eating, the regularity and duration of eating and the activity of watching TV while eating. SUBJECTS/METHODS: A cross-sectional, questionnaire-based internet survey was conducted in April 2012 with stratified random samples of the populations (aged 15-80 years) in Denmark, Finland, Norway and Sweden (N=7531, completion rate 9-13%). The questionnaire elicited detailed accounts of one day of eating focusing on social and practical aspects of eating events. The validated Dietary Quality Score was the dependent variable. This measure is based on eight food frequency questions focusing on fats, vegetables, fruits and fish in the diet. RESULTS: Eating activities were associated with diet quality even when motivation to eat healthily and sociodemographic factors were controlled for. The number of daily eating events and eating main meals was positively correlated with diet quality in all countries. Beyond that, activities that were significantly associated with diet quality varied with country. When measured separately, the association between each activity and diet quality was weaker than motivation to eat healthily, but in combinations that are found in parts of the populations, the association was substantial. CONCLUSIONS: Daily practices related to eating are correlated with diet quality. Practices that are important are in part universal but also country-specific. Efforts to promote healthy eating should address not only cognitive factors but also everyday contexts of eating that facilitate or hamper healthy practices.