Neural dynamics of inflectional and derivational morphology processing in the human brain

We investigated neural distinctions between inflectional and derivational morphology and their interaction with lexical frequency using the mismatch negativity (MMN), an established neurophysiological index of experience-dependent linguistic memory traces and automatic syntactic processing. We presented our electroencephalography (EEG) study participants with derived and inflected words of variable lexical frequencies against their monomorphemic base forms in a passive oddball paradigm, along with acoustically matched pseudowords. Sensor space and distributed source modelling results showed that at 100–150 msec after the suffix onset, derived words elicited larger responses than inflected words. Furthermore, real derived words showed advantage over pseudo-derivations and frequent derivations elicited larger activation than less frequent ones. This pattern of results is fully in line with previous research that explained lexical MMN enhancement by an activation of strongly connected word-specific long-term memory circuits, and thus suggests stronger lexicalisation for frequently used complex words. At the same time, a strikingly different pattern was found for inflectional forms: higher response amplitude for pseudo-inflections than for real inflected words, with no clear frequency effects. This is fully in line with previous MMN results on combinatorial processing of (morpho)syntactic stimuli: higher response to ungrammatical morpheme strings than grammatical ones, which does not depend on the string's surface frequency. This pattern suggests that, for inflectional forms, combinatorial processing route dominates over whole-form storage and access. In sum, our results suggest that derivations are more likely to form unitary representations than inflections which are likely to be processed combinatorially, and imply at least partially distinct brain mechanisms for the processing and representation of these two types of morphology. These dynamic mechanisms, underpinned by perisylvian networks, are activated rapidly, at 100–150 msec after the information arrives at the input, and in a largely automatic fashion, possibly providing neural basis for the first-pass morphological processing of spoken words.     

Influence of physical activity on vertebral strength during late adolescence

Background contextReduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton.PurposeIn this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD.Study designThe association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence.Patient sampleThe study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans.MethodsWe measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance.Results and conclusionsWe observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years.     

Patient radiation dose and fluoroscopy time during ERCP: a single-center,retrospective study of influencing factors

Objectives: Recently, both the number and the complexity with associated increased technical difficulty of therapeutic ERCP procedures have significantly increased resulting in longer procedural and fluoroscopy times. During ERCP, the patient is exposed to ionizing radiation and the consequent radiation dose depends on multiple factors. The aim of this study was to identify factors affecting fluoroscopy time and radiation dose in patients undergoing ERCP.

Materials and methods: Data related to patient demographics, procedural characteristics and radiation exposure in ERCP procedures (n?=?638) performed between August 2013 and August 2015 was retrospectively reviewed and analyzed. Statistically significant factors identified by univariate analyses were included in multivariate analysis with fluoroscopy time (FT) and dose area product (DAP) as dependent variables. Effective dose (ED) was estimated from DAP measurements using conversion coefficient.

Results: The factors independently associated with increased DAP during ERCP were age, gender, radiographer, complexity level of ERCP, cannulation difficulty grade, bile duct injury and biliary stent placement. In multivariate analysis the endoscopist, the complexity level of ERCP, cannulation difficulty grade, pancreatic duct leakage, bile duct dilatation and brushing were identified as predictors for a longer FT. The mean DAP, FT, number of acquired images and ED for all ERCP procedures were 2.33 Gy·cm², 1.84?min, 3 and 0.61 mSv, respectively.

Conclusions: Multiple factors had an effect on DAP and FT in ERCP. The awareness of these factors may help to predict possible prolonged procedures causing a higher radiation dose to the patient and thus facilitate the use of appropriate precautions.     

An evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing methodologies for clinical practice

Ovarian cancer patients with germline or somatic pathogenic variants benefit from treatment with poly ADP ribose polymerase (PARP) inhibitors. Tumor BRCA1/2 testing is more challenging than germline testing as the majority of samples are formalin‐fixed paraffin embedded (FFPE), the tumor genome is complex, and the allelic fraction of somatic variants can be low. We collaborated with 10 laboratories testing BRCA1/2 in tumors to compare different approaches to identify clinically important variants within FFPE tumor DNA samples. This was not a proficiency study but an inter‐laboratory comparison to identify common issues. Each laboratory received the same tumor DNA samples ranging in genotype, quantity, quality, and variant allele frequency (VAF). Each laboratory performed their preferred next‐generation sequencing method to report on the variants. No false positive results were reported in this small study and the majority of methods detected the low VAF variants. A number of variants were not detected due to the bioinformatics analysis, variant classification, or insufficient DNA. The use of hybridization capture or short amplicon methods are recommended based on a bioinformatic assessment of the data. The study highlights the importance of establishing standards and standardization for tBRCA testing particularly when the test results dictate clinical decisions regarding life extending therapies.     

Indentation stiffness of repair tissue after autologous chondrocyte transplantation

Our main hypothesis was that indentation stiffness of the repair tissue approaches the values of adjacent cartilage 1 year after autologous chondrocyte transplantation. We also wanted to investigate the differences between osteochondritic lesions and full-thickness lesions. Thirty patients with cartilage lesions were operated on with autologous chondrocyte transplantation. The repair was evaluated arthroscopically, indentation stiffness was measured, and clinical evaluations were done. The stiffness of the repair tissue improved to 62% (mean 2.04 +/- 0.83 N, mean +/- SD) of adjacent cartilage (3.58 +/- 1.04 N). Fifty-three percent of the patients graded their knee as excellent or good and 47% of the patients graded their knee as fair at the followup. In six patients the normalized stiffness was at least 80%, suggesting hyaline-like repair. The indentation stiffness of the osteochondritis dissecans lesion repairs (1.45 +/- 0.46 N; n = 7) was less than that of the nonosteochondritis dissecans lesion repair sites (2.37 +/- 0.72 N; n = 19). Gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) during followup of four patients suggested proteoglycan replenishment, although all grafts showed low indentation values. Low stiffness values may indicate incomplete maturation or predominantly fibrous repair. The indentation analysis showed that the repair tissue stiffness could, in some cases, reach the same level as the adjacent cartilage, but there was a large variation among the grafts.     

Muscle fiber-type distribution as a predictor of blood pressure: a 19-year follow-up study

The known association between physical activity and low blood pressure may be influenced by inherited characteristics. Skeletal muscle consists of type I (slow-twitch) and type II (fast-twitch) muscle fibers, with proportions highly variable between individuals and mostly determined by genetic factors. A high percentage of type I fibers (type I%) has been associated with low blood pressure in cross-sectional studies. We investigated whether type I percentage predicts future blood pressure levels and explains part of the association between physical activity and blood pressure. At baseline, in 1984, muscle fiber-type distribution, physical activity, and body mass index (BMI) were determined in 64 healthy men (age, 32 to 58 years). At follow-up, in 2003, blood pressure, physical activity, and BMI were determined in these men. In subjects without antihypertensive medication (n=43), type I percentage accounted for 5%/18% of the variation in systolic/diastolic blood pressure. A high type I percentage predicted, independent of both baseline (in 1984) and follow-up (in 2003), physical activity, BMI, and low systolic and diastolic blood pressure. Adjusted for all baseline covariates, a 20-unit higher type I percentage predicted a 11.6-mm Hg lower systolic blood pressure (P=0.018) and a 5.0-mm Hg lower diastolic blood pressure (P=0.018). High levels of physical activity in 1984 predicted low diastolic blood pressure, but this association was lost when type I percentage was included into the model. A high proportion of type I fibers in skeletal muscle is an independent predictor of low blood pressure and explains part of the known association between high levels of physical activity and low blood pressure.     

Occurrence of chronic disease in former top-level athletes. Predominance of benefits,risks or selection effects?

Former elite athletes from most sports disciplines have lower overall morbidity risk and enjoy better self-rated health in later years compared with the general population and matched controls who were healthy at young age. This is seen particularly among former endurance athletes who have a lower incidence of coronary heart disease and type 2 diabetes mellitus. Most often data are available only for men. Based on the available data, participation in elite sports cannot be regarded as an overall health hazard. However, aside from a high risk of acute injury in specific sports, possible negative effects of long-standing athletic activity on the development of osteoarthritis should not be neglected. It should also be remembered that elite athletes are a biologically and genetically select group who are not representative of the population at large. Given the nature of the available data, the possible health consequences of recent changes in different characteristics of sports, such as training practices, professionalism and use of doping, cannot be properly predicted.