Efficacy of a 'functional energy drink' in counteracting driver sleepiness

Driver sleepiness is a major cause of serious road crashes. Coffee is often used as an effective countermeasure to driver sleepiness. However, the caffeine levels in coffee are variable, whereas certain proprietary "functional energy drinks" (FEDs) contain known levels of caffeine (and other ingredients). We investigated the effectiveness of a well-known FED in reducing sleepiness in drivers. Twelve healthy young adults drove an instrumented car simulator between 14:00 and 17:00 h. Their sleepiness was enhanced by sleep restriction to 5 h the night before. Following a pretreatment 30-min drive and at the beginning of a 30-min break, participants were given double-blind 250-ml FED (containing sucrose, glucose, 80-mg caffeine, taurine, glucuronolactone and vitamins) vs. a control drink with the same volume and same taste but without caffeine, taurine and glucuronolactone. Two hours of continuous driving ensued. Lane drifting, subjective sleepiness and the electroencephalogram (EEG) were monitored throughout. Compared with the control, the FED significantly reduced sleep-related driving incidents and subjective sleepiness for the first 90 min of the drive. There was a trend for the EEG to reflect less sleepiness during this period. It was concluded that the FED is beneficial in reducing sleepiness and sleep-related driving incidents under conditions of afternoon monotonous driving following sleep restriction the night before.     

A mouse model of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene. This disorder is characterized by degeneration of motor and sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as gynecomastia and reduced fertility. We describe the development of a transgenic model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR(65)) or 120 CAG repeats (AR(120)), with widespread expression driven by the cytomegalovirus promoter. Mice carrying the AR(120) transgene displayed behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a mild phenotype. Progressive muscle weakness and atrophy was observed in AR(120) mice and was associated with the loss of alpha-motor neurons in the spinal cord. There was no evidence of neurodegeneration in other brain structures. Motor dysfunction was observed in both male and female animals, showing that in SBMA the polyglutamine repeat expansion causes a dominant gain-of-function mutation in the AR. The male mice displayed a progressive reduction in sperm production consistent with testis defects reported in human patients. These mice represent the first model to reproduce the key features of SBMA, making them a useful resource for characterizing disease progression, and for testing therapeutic strategies for both polyglutamine and motor neuron diseases.     

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

Green light attenuates melatonin output and sleepiness during sleep deprivation

Melatonin output covaries with sleepiness, with both peaking early morning. Bright white light suppresses this output, but it is not known if such treatment ameliorates nighttime sleepiness during sleep deprivation. However, sleep-deprived subjects find such light irritating. Humans are particularly sensitive to green light, and melatonin output is more readily suppressed by this hue. A pilot study using different green light regimens showed that sleep-deprived subjects well tolerated 2,000 lux green light given 10 min hourly, and that this dose reduced nighttime melatonin output. The main study gave this light treatment vs. a low intensity red/green light control, from 1900 hr for 11 hr, to two groups of subjects (n = 6 each) sleep deprived for 36 hr. Urine was collected at 6-hr intervals during sleep loss and on a baseline day. Vigilance performance, subjective sleepiness, and oral temperature were monitored during sleep loss. The experimental condition suppressed urine 6-hydroxymelatonin sulfate (aMT6s) output between 0000 hr and 0600 hr, and increased it 0600-1200 hr; but there was no change in total 24-hr values. The control condition had no such effects. The oral temperature rhythm remained unchanged. Vigilance and subjective sleepiness were improved significantly relative to control values during 0000-0600 hr; these improvements were maintained somewhat over the 0600-1200-hr period, contrary to what one might expect if the delayed melatonin surge at this time was increasing sleepiness. Although the bright green light helped counteract sleepiness, any causal link with changes in melatonin output seem tenuous.     

Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

The effects of competition and motor reprogramming on visuomotor selection in unilateral neglect

Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets. To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment 2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements. Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events. Received: 1 October 1996 / Accepted: 21 October 1997     

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.     

Exclusion of the Jefferson salamander,Ambystoma jeffersonianum,from some potential breeding ponds in Pennsylvania: Effects of pH,temperature, and metals on embryonic development

A field survey revealed that Al, SO₄, H⁺, and Zn were significantly higher in 40 ponds lacking successful breeding of the Jefferson salamander, A. jeffersonianum, whereas alkalinity, Cu, DOC, K, Mg, Na, and NO₃ were significantly higher in 10 ponds that supported successful breeding. In a second smaller set of ponds used for transplant studies, Al, conductivity, H⁺, and SiO₂ were significantly higher in five ponds lacking reproduction of A. jeffersonianum; alkalinity, Ca, and K were significantly higher in three ponds with successful reproduction. Survival and hatching success were significantly greater for egg masses transplanted into ponds supporting viable Jefferson salamander populations than into those that did not. Survival and hatching success were greater at 15°C than at 10°C. Low pH slowed developmental rate, consequently increasing the time until hatching. Low pH decreased hatching success of the embryos at 10 and 15°C. Copper was acutely toxic to embryos at pH 4.50 (96 h LC₅₀=315 g/L); chronic exposure levels in the field were much lower (approximately 0.01 times). Since successful ponds actually contained more Cu than unsuccessful ones, Cu does not appear to be toxic in the field. Aluminum ameliorated the acute 96 h toxicity of pH 4.50; at [Al]'s between 250 and 500 g/L mortality at pH 4.50 was greatly reduced. This effect of Al occurred at concentrations comparable to those found in the field. Lead and zinc, at concentrations up to 2,000 g/L, had no apparent effects on the developing embryos of A. jeffersonianum. Aluminum, Pb, and Zn did not afect developmental rate, as did low pH and Cu. Based on these findings, low pH and its interaction with Al are likely to be major factors responsible for the success or failure of the Jefferson salamander in breeding ponds in Pennsylvania. Further investigation is needed into interations among pH, metals, dissolved organics, and non-toxic cations to further clarify the mechanisms of toxicity of the complex mixture of which pond water consists.