Benign neonatal sleep myoclonus in newborn infants of opioid dependent mothers

Objective: The aim of our study was to evaluate the incidence, duration and risk factors for benign neonatal sleep myoclonus (BNSM) in infants with neonatal abstinence syndrome (NAS) treated with opioids or sedatives, compared with control infants.
Methods: This is a single centre observational case control study. Seventy-eight near term and term infants with neonatal opiate abstinence syndrome confirmed by meconium analysis were included. Exclusion criteria were cerebral malformation, intracranial haemorrhage and perinatal asphyxia. The babies were assessed eight hourly with a modified Finnegan score that included sleep myoclonus. Seventy-eight infants not exposed to opiates during pregnancy, hospitalized for at least 14 days and matched for gestational age were used as controls.
Results: The median gestational age was 38 ¹/₇ (95% CI: 35 ³/₇–41 ²/₇) weeks, birth weight 2730 (95% CI: 1890–3600) g, umbilical artery pH 7.25 (CI 7.10–7.37) and Apgar score at 5 minutes 9 (95% CI: 7–10). The control infants did not differ in these characteristics.
Sleep myoclonus was diagnosed in 52 (67%) of the infants with NAS and 2 (2.6%) of the controls (OR 26 [95% CI: 7–223], p < 0.001). Myoclonus appeared as early as day 2 and as late as day 56 of life (median day 6) and lasted for 1 to 93 days (median 13 days). All infants had serum glucose > 2.5 mmol/L at first occurrence. The neurological examinations as well as cerebral ultrasound scans were normal. An electroencephalogram (EEG) carried out in 18 infants showed no signs of epileptic activity.
Conclusion: BNSM has a high incidence in infants with NAS. The diagnosis can be made clinically. In the absence of other neurological symptoms further investigations such as EEG are not necessary and anticonvulsive treatment is not indicated.     

Amphetamine injections into the nucleus accumbens affect neither acquisition/expression of conditioned fear nor baseline startle response

The acoustic startle response is enhanced during states of fear and attenuated during pleasant ones. Our question was whether pharmacological stimulation of the reward system disrupts the learning and retrieval of conditioned fear as measured by fear-potentiated startle. We therefore injected the dopamine agonist amphetamine into the nucleus accumbens (NAC) immediately before either acquisition or expression of conditioned fear and measured the effect of these injections on fear-potentiated startle and baseline startle response. This study clearly showed that amphetamine injections into the NAC had no effect on baseline startle amplitude and acquisition/expression of conditioned fear. In contrast, amphetamine injections into the nucleus accumbens clearly enhanced spontaneous motor activity. These results suggest that dopamine within the NAC is not involved in modulation of fear-potentiated startle and baseline startle.     

Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.     

Optimising the methodology of calculating the cerebral blood flow of newborn infants from near infra-red spectrophotometry data

Cerebral blood flow can be measured in neonates by near infra-red spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to compare the test-retest variability of two previously proposed methods (UCH and COP) of analysis, and to investigate the influence of sampling rates, smoothing and integration periods. Under clinical conditions good measurements are often difficult to obtain. Therefore, a second goal is to find ways of determining the quality of individual measurements. 380 cerebral blood flow measurements from 69 infants are analysed. The data set is optimised statistically for the lowest test-retest variability and the following results are obtained. The test-retest variability of measurements at 2 s sampling time data is considerably worse than at 0·5 s sampling time. Smoothing does not change the test retest variability. A 6 s integration period gives higher values and higher test-retest variability than an 8 s integration period. By applying the suggested criteria, a test-retest variability of 17% is achieved, if 50% of the measurements are rejected. The mean cerebral blood flow is 12·2 ml(100 g)⁻¹ min⁻¹ for the UCH method and 97·7 ml(100 g)⁻¹ min⁻¹ for the COP method. The test-retest variability of both methods is comparable for 0·5 s sampling time. For 2 s sampling time the method proposed by Skov et al. is significantly better. These test retest variabilities represent maximum values, part of the observed variability may be due to physiological changes of unknown magnitude.     

Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization

Huss S, Wardelmann E, Goltz D, Binot E, Hartmann W, Merkelbach‐Bruse S, Büttner R & Schildhaus H‐U (2012) Histopathology  61, 59–68 Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization Aims: Inflammatory fibroid polyps (IFP) are mesenchymal tumours of the gastrointestinal tract. This study was performed to broaden the base of evidence of the pathogenic role of PDGFR mutations in IFP with particular regard to clinicopathological data and mutational patterns among IFP subtypes. Methods and results: Molecular analysis of 38 tumours revealed activating mutations in three different exons of PDGFRA in 25 IFP. For the first time we report two cases with PDGFRA‐exon 14 mutations (p.N659K; p.[N659K(+)T665A]). The results of our study and cases reported earlier indicate clearly that there is a localization‐specific pattern: exon 12 mutations predominate in the small intestine, while exon 18 mutations occur frequently in the stomach (P < 0.001). Codons 567–571 of PDGFRA represent an IFP specific mutational hot spot and are affected most frequently by deletions. Furthermore, in our series IFP of the stomach share common features. In contrast to intestinal IFP, gastric tumours occur at higher age, show heavy inflammation and tend to be smaller. IFP located in the small intestine are frequently associated with intussusception. Conclusion: We conclude that there is a ‘small bowel’ and a ‘gastric’ phenotype of IFPs which are associated with exon 12 and exon 18 PDGFRA mutations, respectively.     

Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon

Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent.     

Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model

BACKGROUND: Research suggests that low-grade psychotic experiences in the general population are a common but transitory developmental phenomenon. Using two independent general population samples, the hypothesis was examined that common, non-clinical developmental expression of psychosis may become abnormally persistent when synergistically combined with developmental exposures that may impact on behavioural and neurotransmitter sensitization such as cannabis, trauma and urbanicity. METHOD: The amount of synergism was estimated from the additive statistical interaction between baseline cannabis use, childhood trauma and urbanicity on the one hand, and baseline psychotic experiences on the other, in predicting 3-year follow-up psychotic experiences, using data from two large, longitudinal, random population samples from the Netherlands [The Netherlands Mental Health Survey and Incidence Study (NEMESIS)] and Germany [The Early Developmental Stages of Psychopathology (EDSP) study]. RESULTS: The 3-year persistence rates of psychotic experiences were low at 26% in NEMESIS and 31% in EDSP. However, persistence rates were progressively higher with greater baseline number of environmental exposures in predicting follow-up psychotic experiences (chi2=6.9, df=1, p=0.009 in NEMESIS and chi2=4.2, df=1, p=0.04 in EDSP). Between 21% and 83% (NEMESIS) and 29% and 51% (EDSP) of the subjects exposed to both environmental exposures and psychotic experiences at baseline had persistence of psychotic experiences at follow-up because of the synergistic action of the two factors. CONCLUSION: The findings suggest that environmental risks for psychosis act additively, and that the level of environmental risk combines synergistically with non-clinical developmental expression of psychosis to cause abnormal persistence and, eventually, need for care.     

Physical activity and prevalence and incidence of mental disorders in adolescents and young adults

BACKGROUND: Although positive effects of physical activity on mental health indicators have been reported, the relationship between physical activity and the development of specific mental disorders is unclear. METHOD: A cross-sectional (12-month) and prospective-longitudinal epidemiological study over 4 years in a community cohort of 2548 individuals, aged 14-24 years at outset of the study. Physical activity and mental disorders were assessed by the DSM-IV Composite International Diagnostic Interview (CIDI) with an embedded physical activity module. Multiple logistic regression analyses controlling for age, gender and educational status were used to determine the cross-sectional and prospective associations of mental disorders and physical activity. RESULTS: Cross-sectionally, regular physical activity was associated with a decreased prevalence of any and co-morbid mental disorder, due to lower rates of substance use disorders, anxiety disorders and dysthymia. Prospectively, subjects with regular physical activity had a substantially lower overall incidence of any and co-morbid mental disorder, and also a lower incidence of anxiety, somatoform and dysthymic disorder. By contrast, the incidence of bipolar disorder was increased among those with regular physical activity at baseline. In terms of the population attributable fraction (PAF), the potential for preventive effects of physical activity was considerably higher for men than for women. CONCLUSIONS: Regular physical activity is associated with a substantially reduced risk for some, but not all, mental disorders and also seems to reduce the degree of co-morbidity. Further examination of the evidently complex mechanisms and pathways underlying these associations might reveal promising new research targets and procedures for targeted prevention.