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Accumulating evidence suggests that deficits of visual selective attention may already occur at early stages of Alzheimer's disease (AD) like the prodromal phase of mild cognitive impairment (MCI).
Our study investigated visual selective attention in amnestic MCI and probable AD patients compared to healthy elderly controls. Groups were matched for age, gender and education. In combination with Bundesen's ‘theory of visual attention’, two mathematically independent and quantitative parameter estimates were derived from a partial report of briefly presented letter arrays: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and right hemifield.
Compared to controls, MCI patients showed significantly reduced top-down controlled selection which further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. The majority of patients was biased to the left. Across MCI and AD patients, carriers of the apolipoprotein E ɛ4 allele (ApoE4) revealed a leftward spatial bias. The leftward bias was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. ApoE4-negative subjects showed balanced attentional weighting.
These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal cortico-cortical networks. Accompanying, an early interhemispheric asymmetry in temporo-parietal cortical interactions might cause a pathological spatial bias. As the inheritance of ApoE4 is associated with asymmetric parietal metabolism, a pathological spatial bias may function as early cognitive marker for detecting probable AD subjects.
Schizophrenia is often accompanied by cognitive dysfunctions. Post-mortem and in vivo studies have revealed increased cortical 5-HT1A-receptor density and it was assumed that 5-HT1A-receptor active drugs could enhance cognition. Moreover, partial 5-HT1A-receptor agonists positively affected verbal memory in schizophrenic patients. However, the role of the 5-HT1A-receptor for cognition has not been fully clarified.
Recently, we have introduced transgenic mice overexpressing the 5-HT1A-receptor postsynaptically in the cortex and hippocampus. Function of the surplus receptors was verified by receptor activation with the agonist 8-OH-DPAT.
In this study we further investigated the role of postsynaptic 5-HT1A-receptors for cognition. Therefore, our mice were tested in the inhibitory avoidance, Morris water maze, and hole-board habituation task. Moreover, the effects of low and high doses of 8-OH-DPAT were examined in the inhibitory avoidance task.
Our transgenic mice showed no overall cognitive deficit. As a tendency, inhibitory avoidance retention was impaired in transgenic mice compared to wild-type controls. Both genotypes showed similar spatial learning abilities in the Morris water maze and habituated to the hole-board in a comparable manner. Anterograde amnesia induced by 8-OH-DPAT was in transgenic mice already apparent in a third of the dose used for wild-type mice. Retrograde amnesia could not be triggered.
Since the transgenic mice show untreated a rather normal behaviour, we assume that they possess compensatory mechanisms. However, after activation of the postsynaptic 5-HT1A-receptors the differences between wild-type and transgenic mice became more clear. Hence, our findings suggest that the cortical and hippocampal 5-HT1A-receptors play rather a modulatory role in learning.
The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition.
Methods
The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates.
Results
There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs.
Conclusions
Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.
Prebiotic oligosaccharides, including galacto-oligosaccharides (GOS), are used in infant formula to mimic human milk oligosaccharides, which are known to have an important role in the development of the intestinal microbiota and the immune system in neonates. The maturation of the intestines in piglets closely resembles that of human neonates and infants. Hence, a neonatal piglet model was used to study the multi-faceted effect of dietary GOS in early life. Naturally farrowed piglets were separated from the mother sow 24–48 h postpartum and received a milk replacer with or without the addition of GOS for 3 or 26 d, whereafter several indicators of intestinal colonisation and maturation were measured. Dietary GOS was readily fermented in the colon, leading to a decreased pH, an increase in butyric acid in caecum digesta and an increase in lactobacilli and bifidobacteria numbers at day 26. Histomorphological changes were observed in the intestines of piglets fed a GOS diet for 3 or 26 d. In turn, differences in the intestinal disaccharidase activity were observed between control and GOS-fed piglets. The mRNA expression of various tight junction proteins was up-regulated in the intestines of piglet fed a GOS diet and was not accompanied by an increase in protein expression. GOS also increased defensin porcine β-defensin-2 in the colon and secretory IgA levels in saliva. In conclusion, by applying a neonatal piglet model, it could be demonstrated that a GOS-supplemented milk replacer promotes the balance of the developing intestinal microbiota, improves the intestinal architecture and seems to stimulate the intestinal defence mechanism.
Vegetable production systems are often characterized by excessive nitrogen (N) fertilization and the incorporation of large amounts of post-harvest crop residues. This makes them particularly prone to ammonia (NH3) and nitrous oxide (N2O) emissions. Yet, urgently needed management strategies that can reduce these harmful emissions are missing, because underlying processes are not fully understood. The present study therefore focuses on the effects of residue placement on NH3 and N2O emissions. For this, cauliflower leaf residues (286 kg N/ha) were either applied as surface mulch (mulch) or mixed with the topsoil (mix) and in situ NH3 and N2O emissions were investigated. The experiment took place on a sandy soil in Northeastern Germany during summer 2012. Residue application created a high peak in N2O emissions during the first 2 weeks, irrespective of residue placement. There was no significant difference in the emission sums over the experimental period (65 days) between the mix (5·8 ± 0·68 kg N2O-N/ha) and the mulch (9·7 ± 1·53 kg N2O-N/ha) treatment. This was also the case for NH3 emissions, which exhibited a lower initial peak followed by a prolonged decline. Measured emission sums were 4·1 ± 0·33 (mix) and 5·1 ± 0·73 (mulch) kg NH3-N/ha. It was concluded that substantial NH3 and N2O emissions can occur after high input of available organic carbon and N even in a coarse-textured soil with low water-holding capacity. Other than expected, surface-application does not enhance NH3 emissions at the expense of N2O emissions compared with residue mixing into the soil, at least under the conditions of the present study.
Converging evidence indicates that a considerable amount of variance in self-estimated emotional competency can be directly attributed to genetic factors. The current study examined the associations between the polymorphisms of the Catechol-O-methyltransferase (COMT Met158Val) and the serotonin transporter (5-HTTLPR) and specific measures of the self-estimated effectiveness of an individual’s emotion perception and regulation. Emotional competence was measured in a large sample of 289 healthy women by using the Self-report Emotional Ability Scale (SEAS), which includes two subscales for the assessment of emotion perception and regulation in the intra-personal domain and two subscales for the assessment of emotion perception and regulation in the inter-personal domain. Participants’ reports of effective emotion regulation in everyday life were associated with the COMT Met-allele, with women homozygous for the Val-allele scoring lowest on this scale. Self-estimated effectiveness of emotion perception of the individual’s own emotions was related to the 5-HTTLPR. Both homozygous groups (s/s and l/l) rated their intra-personal emotion perception less effective than participants in the heterozygous s/l group. Taken together, the results indicate that genetic variants of the COMT and 5HTTLPR genes are differentially associated with specific measures of the self-estimated effectiveness of an individual’s emotion perception and regulation in the intra-personal domain. (JINS, 2014, 20, 1–9)
Edited by
Alex S. Evers, Washington University School of Medicine, St Louis,Mervyn Maze, University of California, San Francisco,Evan D. Kharasch, Washington University School of Medicine, St Louis
Electroconvulsive therapy (ECT) is an effective treatment for major
depression. Optimising efficacy and minimising cognitive impairment are
goals of ongoing technical refinements.
Aims
To compare the efficacy and cognitive effects of a novel electrode
placement, bifrontal, with two standard electrode placements, bitemporal
and right unilateral in ECT.
Method
This multicentre randomised, double-blind, controlled trial (NCT00069407)
was carried out from 2001 to 2006. A total of 230 individuals with major
depression, bipolar and unipolar, were randomly assigned to one of three
electrode placements during a course of ECT: bifrontal at one and a half
times seizure threshold, bitemporal at one and a half times seizure
threshold and right unilateral at six times seizure threshold.
Results
All three electrode placements resulted in both clinically and
statistically significant antidepressant outcomes. Remission rates were
55% (95% CI 43–66%) with right unilateral, 61% with bifrontal (95% CI
50–71%) and 64% (95% CI 53–75%) with bitemporal. Bitemporal resulted in a
more rapid decline in symptom ratings over the early course of treatment.
Cognitive data revealed few differences between the electrode placements
on a variety of neuropsychological instruments.
Conclusions
Each electrode placement is a very effective antidepressant treatment
when given with appropriate electrical dosing. Bitemporal leads to more
rapid symptom reduction and should be considered the preferred placement
for urgent clinical situations. The cognitive profile of bifrontal is not
substantially different from that of bitemporal.
The development of language and communication may play an important role in the emergence of behavioral problems in young children, but they are rarely included in predictive models of behavioral development. In this study, cross-sectional relationships between language, attention, and behavior problems were examined using parent report, videotaped observations, and performance measures in a sample of 116 severely and profoundly deaf and 69 normally hearing children ages 1.5 to 5 years. Secondary analyses were performed on data collected as part of the Childhood Development After Cochlear Implantation Study, funded by the National Institutes of Health. Hearing-impaired children showed more language, attention, and behavioral difficulties, and spent less time communicating with their parents than normally hearing children. Structural equation modeling indicated there were significant relationships between language, attention, and child behavior problems. Language was associated with behavior problems both directly and indirectly through effects on attention. Amount of parent–child communication was not related to behavior problems.
Francisella tularensis was identified as the cause of a die-off which occurred among a colony of semi-free-living common marmosets (Callithrix jacchus). During the outbreak 5 out of 62 animals died of tularaemia in a research facility located in the district of Goettingen, Germany. All animals had been born at the facility suggesting an endemic infection. A total of five culture isolates were recovered and characterized as F. tularensis holarctica, biovar I. These cultures represent the first isolates obtained in the Federal Republic of Germany for more than 45 years. The outbreak area shows several geographical and ecological characteristics known to favour long-term presence of F. tularensis. Persistence of the pathogen in the remote region along the former German–German border, continuous re-introduction from eastern European countries after destruction of the ‘Iron curtain’ or introduction through migrating birds are testable hypotheses which could explain the emergence of tularaemia in this particular region.
This study compared the prevalence and intensity of infections of helminths in 2 chicken breeds in Vietnam, the indigenous Ri and the exotic Luong Phuong. Also, possible correlations with the Major Histocompatibility Complex (MHC) were tested. The most prevalent helminths were Ascaridia galli, Heterakis beramporia, Tetrameres mothedai, Capillaria obsignata, Raillietina echinobothrida and Raillietina tetragona. Differences in prevalence and intensity of infection were found between the 2 breeds. Comparing the 2 groups of adult birds, Ri chickens were observed to have higher prevalence and infection intensities of several species of helminths, as well as a higher mean number of helminth species. In contrast, A. galli and C. obsignata were shown to be more prevalent in Luong Phuong chickens. Furthermore, an age-dependent difference was indicated in the group of Ri chickens in which the prevalence and the intensity of infection was higher for the adult than the young chickens for most helminths. The most notable exception was the significantly lower prevalence and intensities of A. galli in the group of adult chickens. In contrast, the prevalence and intensity were very similar in both age groups of Luong Phuong chickens. Using a genetic marker located in the MHC, a statistically significant correlation between several MHC haplotypes and the infection intensity of different helminth species was inferred. This is the first report of an association of MHC haplotype with the intensity of parasite infections in chickens.