Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway

Recent data have revealed that soluble oligomeric amyloid-beta peptide (Abeta) may be the proximate effectors of neuronal injuries and death in Alzheimer's disease (AD) by unknown mechanisms. Consistently, we recently demonstrated the critical role of a redox-sensitive cytosolic calcium-dependent phospholipase A2 (cPLA2)-arachidonic acid (AA) pathway in Abeta oligomer-induced cell death. According to the involvement of oxidative stress and polyunsaturated fatty acids like AA in the regulation of sphingomyelinase (SMase) activity, the present study underlines the role of SMases in soluble Abeta-induced apoptosis. Soluble Abeta oligomers induced the activation of both neutral and acidic SMases, as demonstrated by the direct measurement of their enzymatic activities, by the inhibitory effects of both specific neutral and acidic SMase inhibitors, and by gene knockdown using antisense oligonucleotides. Furthermore, soluble Abeta-mediated activation of SMases and subsequent cell death were found to be inhibited by antioxidant molecules and a cPLA2-specific inhibitor or antisense oligonucleotide. We also demonstrate that sphingosine-1-phosphate is a potent neuroprotective factor against soluble Abeta oligomer-induced cell death and apoptosis by inhibiting soluble Abeta-induced activation of acidic sphingomyelinase. These results suggest that Abeta oligomers induce neuronal death by activating neutral and acidic SMases in a redox-sensitive cPLA2-AA pathway.     

'One night' sleep deprivation stimulates hippocampal neurogenesis

Neurogenesis in the adult hippocampus can be up- or downregulated in response to a variety of physiological and pathological conditions. Among these, dysregulation of hippocampal neurogenesis has been recently implicated in the pathogenesis of depression. In addition, in animal models of depression, a variety of antidepressant treatments reverse that condition by increasing neurogenesis. As one night sleep deprivation is known to improve mood in depressed patients for at least 1 day, we investigated whether a comparable treatment may affect hippocampal neurogenesis in adult rats. Accordingly, rats were sleep-deprived by gentle handling for 12 h during their physiological period of rest, and were injected with bromodeoxyuridine 4 h and 2 h before the end of sleep deprivation. They were then perfused immediately thereafter, or after 15 days and 30 days. We found that 12 h sleep deprivation significantly increased cell proliferation and the total number of surviving cells in the hippocampal dentate gyrus soon after sleep deprivation, as well as 15 days and 30 days later, in comparison to control rats allowed to sleep. No changes were instead found in the subventricular zone of the lateral ventricles, indicating that 12 h sleep deprivation selectively triggers neurogenic signals to the hippocampus. The present data include acute sleep deprivation among the conditions which upregulate hippocampal neurogenesis and raise the possibility that such response could be implicated in the beneficial effects elicited in depressed patients by one night sleep deprivation. Thus, the findings could contribute to the understanding of the intriguing relationship between depression and neurogenesis in the adult brain.     

Classical lissencephaly associated with dolichocephaly, hair and nail defect

We report on an 1-day-old boy with classical lissencephaly (grade 1, according to Kato and Dobyns, 2003) associated with an extended phenotype, including dolichocephaly, and hair and nail defects. The diagnosis of lissencephaly was made in utero, allowing the rapid characterization of the phenotype at birth. Because previously reported cases were not associated with the features described in our proband, they might represent a newly identified condition.     

Reproducibility of hepatic fat fraction measurement by magnetic resonance imaging

Purpose:

To evaluate the reproducibility of magnetic resonance imaging (MRI)‐determined hepatic fat fraction (%) across imaging sites with different magnet types and field strength. Reproducibility among MRI platforms is unclear, even though evaluating hepatic fat fractions (FFs) using MRI‐based methods is accurate against MR spectroscopy.

Materials and Methods:

Overweight subjects were recruited to undergo eight MRI examinations at five imaging centers with a range of magnet manufacturers and field strengths (1.5 and 3 T). FFs were estimated in liver and in fat‐emulsion phantoms using three methods: 1) dual‐echo images without correction (nominally out‐of‐phase [OP] and in‐phase [IP]); 2) dual‐dual‐echo images (two sequences) with T2* correction (nominally OP/IP and IP/IP); and 3) six‐echo images with spectral model and T2* correction, at sequential alternating OP and IP echo times (Methods 1, 2, and 3, respectively).

Results:

Ten subjects were recruited. For Methods 1, 2, and 3, respectively, hepatic FF ranged from ?2.5 to 27.0, 1.9 to 29.6, and 1.3 to 34.4%. Intraclass correlation coefficients were 0.85, 0.89, and 0.91 for each method, and within‐subject coefficients of variation were 18.5, 9.9, and 10.3%, respectively. Mean phantom FFs derived by Methods 2 and 3 were comparable to the known FF for each phantom. Method 1 underestimated phantom FF.

Conclusion:

Methods 2 and 3 accurately assess FF. Strong reproducibility across magnet type and strength render them suitable for use in multicenter trials and longitudinal assessments. J. Magn. Reson. Imaging 2013;37:1359–1370. © 2012 Wiley Periodicals, Inc.

     

Patent ductus arteriosus in preterm infants is associated with cardiac autonomic alteration and predominant parasympathetic stimulation

Background

Hemodynamic disorders in patent ductus arteriosus (PDA) may alter the stimulation of the autonomic nervous system.

Aim

The objective of this study was to analyze the orthosympathetic–parasympathetic balance in preterm infants with PDA.

Study design and subjects

Patients were included from consecutive admissions to Amiens University Hospital from 2009 to 2011. We defined a PDA group and a Control group (echographic criteria). For each patient, three 4-minutes segments of ECG were recorded during quiet sleep and the RR chronologic series were extracted, and spectral (Fourier Transform) and time-domain analyses were performed. For each parameter of heart rate variability (HRV), average of three measures was determined and analysed.

Results

Forty-four patients were included for analysis. The total HRV power, LF/HF ratio and SDNN were lower in the PDA group (n = 22, gestational age 28.2 w ± 1.9) than in the Control group (n = 22, gestational age 28.8 w ± 2). The decrease in LF power destabilized the autonomic balance in favour of parasympathetic stimulation. After adjustment for postconceptional age, PDA was still associated with parameters of autonomic neural stimulation.

Conclusion

These results suggest association of PDA with predominance of parasympathetic stimulation in preterm infants. The mechanisms of homeostasis in patients with PDA are very complex and involve both circulatory adaptations and control by autonomic pathway. If confirmed, our results could be interesting for future researches aiming to verify the interest of new targeted therapies for the management of PDA.     

Cremated human remains: is measurement of the lateral angle of the meatus acusticus internus a reliable method of sex determination?

The purpose of this study was to evaluate the lateral angle (LA) method—based on the measurement of the angle at which the internal acoustic canal opens up to the surface of the petrous bone—for sex determination in cremated skeletal remains of Italians. The sample consisted of 160 adult individuals of known age and sex who had recently died and were cremated in the crematorium of Ferrara (northern Italy). Several studies have demonstrated that the petrous portion of the temporal bone may be a valuable tool for sex diagnosis in unburned skeletal remains. Since petrous bones are usually preserved after cremation, this method could be of particular interest in the case of burned skeletal remains. The repeatability of intra- and inter-observer measurements was good. The results indicated that male and female lateral angles were significantly different but that the values did not differ among age-groups. There was no bilateral difference in LA. However, neither the 45° angle, proposed in earlier studies as the sectioning point for this variable from male and female data distributions, nor another angular value allowed satisfactory discrimination between the sexes in our sample. The influence of the “age” factor (about 82 % of females were of ≥75 years of age) on the results is critically discussed. The results of this study suggest that the LA method is not sufficiently reliable to assess the sex of elderly Italian individuals from their burned remains and thus should only be used in conjunction with other sexing techniques.     

Postural responses without versus with acute external cervical spine fixation: a comparative study in healthy subjects and patients with acute unilateral vestibular loss

Using a diagnostic prospective cohort single center study design, the influence of a cervical collar on standing balance during dynamic postural perturbations in healthy adults and patients with acute unilateral vestibular dysfunction was measured in 31 healthy subjects and 27 patients with acute unilateral vestibular loss. The main outcome measures were completed standard protocols on the Sensory Organization Test (SOT) and Motor Control Test (MCT) of the NeuroCom Equitest^® computerized posturography platform measured without and with acute cervical fixation, respectively. Paired t test showed no significant difference during the six conditions of neither the SOT scores nor analyzing the SOT strategies or during the MCT between the non-fixed and fixed neck in healthy subjects and in the patients (all p > 0.05). Older healthy subjects showed decreased SOT scores but equal MCT results. The age effect was more dominant in the patients when wearing the collar. Gender had no influence whether in healthy individuals nor in patients. In almost all conditions of the SOT but only in some MCT subtests patients had significantly lower scores than healthy subjects without collar and with collar (all p < 0.05). In conclusion, the SOT but only some subtest of the MCT could clearly distinguish between healthy adults and patient with acute unilateral vestibular loss. Equilibrium scores did not change significantly when the cervical spine was fixed with a collar. Acute fixation of the neck with a collar seems not to affect standing balance, even not when vestibular, visual and/or somatosensory input are also reduced.     

Rate pitch discrimination in cochlear implant users with the use of double pulses and different interpulse intervals

The rate pitch discrimination ability of cochlear implant (CI) users is poor compared to normal-hearing (NH) listeners. At low pulse rates, the just noticeable difference (JND) is on average 20% of the base rate, while NH listeners can discriminate small frequency differences of 0.2% at 1?kHz. Recent investigations suggest that double pulses with short interpulse intervals (IPIs) may have a beneficial effect on rate pitch discrimination in CI users. In a first experiment psychophysical tests were carried out to establish whether rate pitch in CI users could be improved by applying double pulses with equal amplitude and short IPIs. Pulse trains with base rates of 200 and 400?pps, composed of either single pulses or double pulses with IPIs of 15, 50, and 150?μs were presented. In a second experiment pairwise comparisons were carried out between pitch of a pulse train composed of alternating double and single pulses with pitch of pulse trains composed of single pulses. The alternating pulse train had a base rate of 400?pps, the pulse trains with solely single pulses had base rates of 200, 300, and 400?pps. The loudness and pitch perception of the different stimulus types were evaluated and compared. A significant loudness difference was found between single and double pulses for both pulse rates. The JND for pitch discrimination between double-pulse IPIs had a high inter-subject variability, and no significant group effect was found. No subject reported a pitch change between double pulse and single pulse stimulation. In contrast, most of the subjects recognized a change in pitch between single-pulse trains and pulse trains with alternating double and single pulses. The latter was lower in pitch than the single-pulse train stimulation. To conclude, using (equal amplitude) double pulses instead of single pulses in a pulse train does not effect pitch perception. Instead, loudness differs between double pulses and single pulses with the same amplitude.     

Tunisian Women's Perceptions of Desirable Body Size and Chronic Disease Risk

The purpose of this study was to assess attitudes towards body size of urban Tunisian women. Firstly, to determine body size satisfaction amongst women and investigate the body size that women associate with good health, high social status and individual desirability; and secondly, to study whether perception varies in different groups of society, to see if there is a difference of attitudes in younger women and those of higher socioeconomic status. A cross-sectional, population based study was conducted in a peri-urban area of the capital, Tunis with 203 randomly selected women, aged 18–52 years. They were asked to associate 31 items with 1 of 6 photographic silhouettes of different body size; BMI was measured and over half of women were overweight or obese (BMI ≥ 25kg/m²). Almost two-thirds of all women were dissatisfied with their current body size. A normal body size (BMI 20–24 kg/m²) was seen in the most positive light by Tunisian women, although some positive attributes were associated with overweight silhouettes. Obesity was seen as undesirable, associated with greediness and poor health. There was no marked preference by younger women for slimmer body sizes, as had been expected. However, there was a preference by women with higher socioeconomic status for slimmer body sizes for some items. The finding that Tunisian women did not prefer larger body sizes may suggest a preference for a slimmer norm, closer to that in Western societies.