Chronic stress undermines the compensatory sleep efficiency increase in response to sleep restriction in adolescents

To investigate the effects of real‐life stress on the sleep of adolescents, we performed a repeated‐measures study on actigraphic sleep estimates and subjective measures during one regular school week, two stressful examination weeks and a week's holiday. Twenty‐four adolescents aged 17.63 ± 0.10 years (mean ± standard error of the mean) wore actigraphs and completed diaries on subjective stress, fatigue, sleep quality, number of examinations and consumption of caffeine and alcohol for 4 weeks during their final year of secondary school. The resulting almost 500 assessments were analysed using mixed‐effect models to estimate the effects of mere school attendance and additional examination stress on sleep estimates and subjective ratings. Total sleep time decreased from 7:38 h ± 12 min during holidays to 6:40 h ± 12 min during a regular school week. This 13% decrease elicited a partial compensation, as indicated by a 3% increase in sleep efficiency and a 6% decrease in the duration of nocturnal awakenings. During examination weeks total sleep time decreased to 6:23 h ± 8 min, but it was now accompanied by a decrease in sleep efficiency and subjective sleep quality and an increase in wake bout duration. In conclusion, school examination stress affects the sleep of adolescents. The compensatory mechanism of more consolidated sleep, as elicited by the sleep restriction associated with mere school attendance, collapsed during 2 weeks of sustained examination stress.     

Number Magnitude Processing and Verbal Working Memory in Children with Mild Intellectual Disabilities

ABSTRACT

This study examined if children (M_age = 14.60) with Mild Intellectual Disabilities (MID) display weaknesses in number processing and verbal working memory. An age-matched and mental age-matched (MA, M_age = 6.17) design extended by a group of 9–10-year-olds, and a group of 11–12-year-olds were used. The MID children’s working memory was equal to the MA group but poorer than the other groups. On number tasks, the MID group was faster than the MA group but slower than the other groups. All groups obtained equal Weber fraction scores and distance effects on the number comparison tasks. The MID group performed subitizing and counting faster than the MA group, but slower than the 11–12-year-olds. The results demonstrate that number processing and working memory in children with MID is characterized by a developmental delay, not a deficit. Their main problem is to access the quantitative meaning of Arabic numerals. The development of different types of cognitive abilities is differently affected by educational experience and intellectual ability. The innate number system appears to be unaffected by intellectual capacity or educational experience, while the innate working memory ability is affected by intellectual capacity but not by educational experience. Culturally acquired symbolic number abilities are strongly affected by educational experience.     

Hand dominancy—A feature affecting sensitivity to pain

Hand dominancy (i.e. handedness) is a factor that should be considered for further characterizing individual variations in sensitivity to pain. The aim of the present study was to examine the contribution of handedness and gender to sensitivity to tonic cold pain in healthy subjects. Participants were 109 healthy volunteers (52 males and 57 females), of whom 65 were right-handed and 44 left-handed. Subjects were exposed to the cold pressor test (1 °C) for both hands while measuring the cold pain threshold, intensity, and tolerance. No significant differences were found in pain threshold or intensity between the right versus the left hands among either the right-handed or the left-handed subjects. However, among the right-handed subjects only, cold pain tolerance was significantly longer in the right hand than in the left hand (32.9 ± 5.1 s vs. 27.0 ± 4.2 s, respectively; p = 0.018). Significant differences were found between males and females in pain threshold, but not in pain intensity or tolerance, either when their right or left hand was tested (p = 0.027 and p = 0.009, respectively). Analyzing pain perception by handedness and gender revealed that the right-handed males were less sensitive to pain in their right versus their left hand, as determined by lower pain intensity (p = 0.031) and longer tolerance (p = 0.047). No significant differences were found among the left-handed males or among the females. The results provide further evidence that handedness is one vital feature that should be considered more often when designing a psychophysical study. This may lead towards improving the translation of laboratory research findings to the clinical setting.     

Prevalence and correlates of tobacco use among Russian cancer patients: Implications for the development of smoking cessation interventions at a cancer center in Russia

This study examined the rate of smoking among 399 cancer patients in Russia and assessed correlates of tobacco use and readiness to quit smoking. The results indicated that (a) 41.6% of patients were smokers; and (b) smokers were likely to be male, have lung or colorectal cancer, exhibit low levels of knowledge concerning the negative effects of smoking, report a low level of advantages to quitting smoking and a high level of disadvantages to quitting smoking, show low perceived risk for the adverse effects of smoking, and exhibit high fatalistic beliefs. Though certain findings converge well with data collected from U.S. samples of cancer patients, these results can guide the development of smoking interventions that address the specific needs of Russian cancer patients. In sum, this study fills a critical gap in knowledge concerning the epidemic of tobacco use in Russia and broadens research regarding tobacco use by cancer patients from the United States to the Russian Federation. Support for this study was provided by National Institutes of Health grant CA95678 (R. Schnoll) and by a U.S. federal appropriation to the American-Russian Cancer Alliance.     

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks,chromosomal instability,and reduced life span in mice

The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51.     

Experimental encephalomyelitis induces changes in DJ-1: implications for oxidative stress in multiple sclerosis

DJ-1 plays an important role in oxidative stress, and is involved in various neurodegenerative diseases. Accumulating evidence suggests a central role for oxidative stress in multiple sclerosis (MS). The aim of this study was to examine whether changes occur in DJ-1 expression in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and protein expression levels in EAE and a correlation between disease severity and increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells. Immunocytochemical staining demonstrated that DJ-1 is present both in the cytoplasm and the nuclei of these cells. This is the first report of modulation of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar results were observed in glioma cells exposed to ROS. In view of the accumulating evidence on the central role of oxidative stress in MS, and the importance of DJ-1 in oxidative stress management by the CNS, we believe that DJ-1 will be found to have a central role in MS.     

Responses of the human auditory cortex to changes in one versus two stimulus features

Neuromagnetic responses were recorded with a 24 SQUID magnetometer in two oddball experiments to determine whether mismatch responses to changes in single stimulus features are additive. In experiment 1, the one feature deviants differed from standards in interstimulus interval (ISI) or frequency, and the two feature deviants in both ISI and frequence. In experiment 2, deviants differed in duration, frequency, or both. All deviants evoked a mismatch field (MMF) with sources close to each other in the supratemporal auditory cortex. Except for the ISI deviants, the MMF sources were about 1 cm anterior to the source of the 100ms response, N100m, to the standards. In the two experiments, MMFs obtained in response to the two feature deviants resembled closely the sum of MMFs in response to one feature deviants. The results suggest that the standards leave a multiple neuronal representation in the human auditory cortex. The particular neuronal traces of the representation react independently to changes in different features of sound stimuli.     

Hanging leg weight--a rapid technique for estimating total body weight in pediatric resuscitation

The accuracy of two methods of rapidly estimating total body weight in children was assessed. The first method correlated patient length to known total body weight, and the second correlated the weight of both legs weighted together to known total body weight. One hundred children undergoing general anesthesia in the operating rooms of Childrens Hospital of Los Angeles were entered into the study. Each child had a known preoperative body weight. After induction of anesthesia, each child's supine length was measured and hanging (inert) legs were weighted. There was excellent linear correlation between hanging leg weight and total body weight (correlation coefficient [r2], 0.95) for all patients, and good linear correlation between supine length and total body weight, r2, 0.86). Range restriction analysis for both techniques showed poor correlation for total body weights of less than 10 kg and poor correlation for the supine length technique when total body weight was more than 25 kg. The hanging leg weight of an inert child has excellent correlation to total body weight for children weighing more than 10 kg.     

Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum

Objectives

To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients.

Methods

Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT.

Results

The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2?±?3.8 and 1.7?±?1.3, respectively (reader1: p?=?0.001, reader2: p?=?0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p?=?0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p?=?0.005 and reader2: p?=?0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7?±?3.4 and 5.6?±?1.5 vessels, respectively (reader1/reader2: p?=?0.02).

Conclusions

We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response.

Key Points

? Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum. ? Formation of highly vascular stroma precedes the actual tumour invasion. ? High macrovascular parameters are associated with node involvement. ? Mesorectal vascular network differs for good and poor responders.