Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX,XYY, or XXY: a systematic review*

Aim To review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs). Method A bibliographic search identified English‐language articles on SCTs. The focus was on studies unbiased by clinical referral, with power of at least 0.69 to detect an effect size of 1.0. Results We identified 35 articles on five neonatally identified samples that had adequate power for our review. An additional 11 studies were included where cases had been identified for reasons other than neurodevelopmental concerns. Individuals with an additional X chromosome had mean IQs that were within broadly normal limits but lower than the respective comparison groups, with verbal IQ most affected. Cognitive outcomes were poorest for females with XXX. Males with XYY had normal‐range IQs, but all three SCT groups (XXX, XXY, and XYY) had marked difficulties in speech and language, motor skills, and educational achievement. Nevertheless, most adults with SCTs lived independently. Less evidence was available for brain structure and for attention, social, and psychiatric outcomes. Within each group there was much variation. Interpretation Individuals with SCTs are at risk of cognitive and behavioural difficulties. However, the evidence base is slender, and further research is needed to ascertain the nature, severity, and causes of these difficulties in unselected samples.     

Differential expression of LAMPs and ubiquitin in human thymus

Lysosome‐associated membrane proteins 1 and 2 (LAMP‐1 and LAMP‐2) are implicated in a variety of normal and pathological processes. LAMP‐2 is proposed to participate in chaperone‐mediated autophagy. Autophagy regulates T‐lymphocyte homeostasis by promoting both survival and proliferation. The biological importance of this process in the thymic gland and especially the involvement of LAMPs are far from being elucidated. The aim of the study was to examine the parallel expression of LAMPs and ubiquitin, a key molecule in autophagy, in normal human thymic glands and thymomas. The immunohistochemical expression of both markers was compared with that of cyclin D1 – an important regulator of cell cycle progression. Novel evidence for differential expression of LAMPs and ubiquitin is presented. Most Hassal's corpuscules in thymoma were negative for LAMPs, but positive in normal thymus. Both lymphocytes and epithelial cells in pathological thymus showed higher intensity for LAMP‐2 compared with LAMP‐1. In thymoma, ubiquitin was more intensively positive in these cell types compared with the normal thymus, suggesting activated autophagy in the course of this pathological state. A deregulation in cyclin D1 expression in thymoma is also reported. The functional importance of these molecules in autoghagy accompanying normal and pathological processes in the thymic gland is reviewed.     

EFFECTS OF AEROBIC CONDITIONING IN LUPUS FATIGUE: A PILOT STUDY

Fatigue, a complex symptom, significantly affects the qualityof life in many patients with systemic lupus erythematosus (SLE).To understand this phenomenon, 23 patients with SLE and fatiguewere studied. Standardized tests of depression (NIMH), fatigue,exercise tolerance (ETT) on a bicycle ergometer, and SLE activitywere obtained. At baseline, SLE patients had significantly lower maximum oxygenconsumption (Vbj max) than normals (p << 0.005). Adjustedfor age and sex, SLE patients perform at 54% of their expectedmaximum Vo₂, which is similar to published data from patientswith rheumatoid arthritis. Depression by NIMH was not correlatedwith Vo₂ max or length of time on ETT. Fatigue measured by Profileof Mood States (POMS) was correlated with ETT time (r = 0.476,p << 0.025) and with Vfoj max (r = –0.402, p <<0.07). After an 8-week aerobic conditioning programme the experimentalgroup increased their aerobic capacity by 19% in contrast to8% in controls. This change correlated with decreased fatigueas measured by visual analogue scales. Exercise did not exacerbatedisease, and only two of 16 experimental subjects experiencedtransient joint symptoms during exercise. KEY WORDS: Systemic lupus erythematosus, Depression, Mood, Oxygen consumption, Aerobic exercise, Fatigue     

The Stability of bFGF Against Thermal Denaturation

Abstract— The influence of sulphated ligand and pH on thermal denaturation of basic fibroblast growth factor (bFGF) was investigated by differential scanning calorimetry (DSC), and verified by fluorescence spectrophotometry. Purity of bFGF before and after heat denaturation was assessed by SDS-PAGE analysis. In DSC studies the samples were heated to 95°C. The midpoint of the temperature change in the thermogram was designated as T_m. Sulphated ligand experiments were undertaken in potassium phosphate (pH 6·5) and sodium acetate buffers. Control thermograms (with no ligand) showed a T_m at 59°C in potassium phosphate buffer. Higher T_m values were noted as sulphated ligand concentration was increased. Similarly when heparin was added, the T_m moved to a higher temperature. A ratio as low as 0·3:1 of heparin to bFGF, increased the T_m to 90°C, which is a 31°C shift in T_m. The effect of pH on thermal denaturation of bFGF was studied in a citrate-phosphate-borate buffer system. A shift in T_m from 46 to 65°C was observed as the pH is changed from 4 to 8. Changes in protein conformation as a function of pH were monitored by fluorescence spectroscopy. It was found that a pH range from 5 to 9 is optimal for the stability of bFGF formulations. In a stability study it was noted that heparin protected bFGF from thermal denaturation only at high temperature.     

Naming norms for brief environmental sounds: Effects of age and dementia

Brief nontonal sounds are used in electrophysiology in the novelty oddball paradigm. These sounds vary in the brain activity they elicit and in the degree to which they can be identified, named, and remembered. Because ease of sound identification may influence sound processing, naming and conceptual norms were determined for 100 sounds for 77 young adults (Experiment 1). Naming ability decreases in normal and pathological aging. Therefore, norms were also derived for older adults (Experiment 2) and for probable Alzheimer's disease patients (Experiment 3). With respect to the young adults, perseverative naming behavior increased in these groups, and sound and picture naming performance were correlated. In Experiment 4, the sound-naming performance of children aged 5–6, 9–11, and 14–16 yers was compared. Name and conceptual agreements improved with age, whereas perseverative behavior decreased. These normative data should be useful in guiding sound selection in future studies and help clarify the relationships between sound naming and other variables, including direct and indirect memory performance.     

THE EFFECTS OF CARBON MONOXIDE ON NEURONS OF THE CEREBELLUM*

The effects of carbon monoxide on neurons of the cerebellum Acute CO exposure in rats produces multifocal edema and neuroglial swelling in cerebellar cortex and nuclei. Chronic multiple daily exposures to CO produce degenerative changes in neurons–shrinkage of cell somata and dendrites, enlargement of nuclei and nucleoli, vacuolation in neuronal cytoplasm, pyknosis and ultimate engulfment by microglia. Focal areas of Purkinje cell loss are typical; individual basket cells and their axons, stellate cells and the deep nuclear neurons are severely affected. Counts of Purkinje cells and their dendritic thorns show reductions of 30% and 31% respectively in affected regions. In foci of severe Purkinje cell loss, dendritic thorns of the neighboring cells which remain assume a greater number of synapses with unusual presynaptic partners, e. g. both parallel fibers and climbing fibers in a single thorn. An increase of 4.2% more synapses per thorn was measured when compared to the normal. Thus, the stress of chronic CO exposure stimulates synaptic plasticity or a compensatory remodelling of neuronal elements in the central nervous system. A scheme is proposed to summarize these changing relationships caused by the loss of some dendritic thorns and the migration of the presynaptic partners to other surviving thorns.     

A STUDY OF ASPIRIN AND NEPENTHE

Two wholetime clinical investigators made a double-blind studyof aspirin and nepenthe, aspirin, nepenthe, and a placebo, inan attempt to define the sensitivity and repeatability of thistype of subjective study. In a total of 1,063 drug administrationsthere was a marked difference between investigators' scoresand evidence of improvement with experience. Investigators'opinions were a more sensitive index than ward staff or patients'opinions. There were few significant side effects. Experimentaldesign and statistical analysis are discussed.