Age, sex, and disease status as determinants of skin hydration and transepidermal water loss among children with and without eczema.

PURPOSE: Skin hydration (SH) and transepidermal water loss (TEWL) are important skin biophysical parameters for assessment of childhood eczema. This study investigated whether age, sex, and disease status influence these parameters. METHODS: Skin hydration and TEWL were measured by Delfin MoistureMeterSC and Delfin Vapometer SWL5, respectively, among children aged ≤18 years with and without eczema. Disease status was evaluated using Scoring Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS) clinical tools. RESULTS: Clinical scores and objective measurements were reviewed for 132 patients with eczema and 120 patients without eczema. In both sexes, SH was significantly higher among children aged ≤2 years with and without eczema than among children aged >2 years with and without eczema. Among children aged >2 years, SH was higher among girls with and without eczema than among boys with and without eczema. Regardless of age or sex, SH was lower among children with eczema than among children without eczema. Age-, sex-, and disease-related differences were not observed for TEWL. Skin hydration was negatively correlated with objective SCORAD (r=-0.418, P<0.001), overall SCORAD (r=-0.385, P<0.001), oedema/papulation (r=-0.243, P=0.041), lichenification (r=-0.363, P=0.002), dryness (r=-0.415, P<0.001), and intensity (r=-0.266, P=0.025). Transepidermal water loss was positively correlated with objective SCORAD (r=0.209, P=0.018), overall SCORAD (r=0.215, P=0.015), and lichenification (r=0.240, P=0.043). Skin hydration was negatively correlated with TEWL among children without eczema (r=-0.401, P<0.001), but not among children with eczema. CONCLUSION: Skin hydration can be used to distinguish clinical differences in eczema based on age, sex, and disease status.

Assessment of dietary food and nutrient intake and bone density in children with eczema.

INTRODUCTION: Dietary restrictions are common among patients with eczema, and such practice may lead to diminished bone mineral density. This study investigated dietary intake and bone mineral density in Hong Kong Chinese children with eczema. METHODS: This cross-sectional and observational study was conducted in a university-affiliated teaching hospital in Hong Kong. Chinese children aged below 18 years with physician-diagnosed eczema were recruited from our paediatric allergy and dermatology clinics over a 6-month period in 2012. Subjects with stable asthma and/or allergic rhinitis who were free of eczema and food allergy as well as non-allergic children were recruited from attendants at our out-patient clinics as a reference group. Intake of various foods and nutrients was recorded using a food frequency questionnaire that was analysed using Foodworks Professional software. Bone mineral density at the radius and the tibia was measured by quantitative ultrasound bone sonometry, and urinary cross-linked telopeptides were quantified by immunoassay and corrected for creatinine level. RESULTS: Overall, 114 children with eczema and 60 other children as reference group were recruited. Eczema severity of the patients was classified according to the objective SCORing Atopic Dermatitis score. Males had a higher daily energy intake than females (median, 7570 vs 6736 kJ; P=0.035), but intake of any single food item or nutrient did not differ between them. Compared with the reference group, children with eczema had a higher intake of soybeans and miscellaneous dairy products and lower intake of eggs, beef, and shellfish. Children with eczema also consumed less vitamin D, calcium, and iron. The mean (standard deviation) bone mineral density Z-score of children with eczema and those in the reference group were 0.52 (0.90) and 0.55 (1.12) over the radius (P=0.889), and 0.02 (1.03) and -0.01 (1.13) over the tibia (P=0.886), respectively. Urine telopeptide levels were similar between the groups. Calcium intake was associated with bone mineral density Z-score among children with eczema. CONCLUSIONS: Dietary restrictions are common among Chinese children with eczema in Hong Kong, who have a lower calcium, vitamin D, and iron intake. Nonetheless, such practice is not associated with changes to bone mineral density or bone resorptive biomarker.

Dairy and nondairy beverage consumption for childhood atopic eczema: what health advice to give?

BACKGROUND: Many parents of children with atopic eczema (AE) practise empirical dietary avoidance and supplementation, and seek healthcare advice on whether consumption of dairy and nondairy beverages may be beneficial or detrimental for this condition. AIM: We investigated if frequency of consumption of beverages was associated with disease severity and quality of life (QoL). METHODS: Parent-reported frequency of drinks and beverages were recorded in consecutive children with AE, and disease severity (Nottingham Eczema Severity Score; NESS), QoL (Children's Dermatology Life Quality Index; CDLQI), skin hydration (SH), transepidermal water loss (TEWL), blood pressure (BP), resting heart rate (RHR) and body mass index (BMI) were evaluated. RESULTS: AE was associated with worse QoL than miscellaneous non-AE skin diseases (P < 0.001). Compared with children without AE, there was a trend for children with AE to drink less milk (P = 0.06) and more miscellaneous beverages (such as Chinese herbal tea and soymilk; P = 0.03). In children with AE, NESS correlated with CDLQI (ρ = 0.66, P < 0.001) and reduced SH (ρ = -0.32, P < 0.001), whereas CDLQI correlated with a higher RHR (ρ = 0.25, P < 0.01). Multiple logistic regression showed that male sex (OR = 0.44, 95% CI 0.20-0.97; P = 0.04) and drinking fresh milk (OR = 0.42, 95% CI 0.20-0.93; P = 0.03) were independent factors associated with less severe disease. Moderate to severe impairment of CDLQI was associated with NESS (OR = 1.48, 95% CI 1.28-1.71; P < 0.001) and RHR (OR = 1.05, 95% CI 1.02-1.08; P < 0.01) but not with reported habits of beverage consumption. Concerning cardiovascular health in AE, frequency of formula milk consumption was associated with RHR (ρ = 0.17, P = 0.04), and soft drink consumption was associated with higher systolic blood pressure (SBP) (ρ = 0.18, P = 0.04). CONCLUSION: This study provides evidence for parental/patient guidance. Children with AE who reported more fresh milk consumption had less severe disease. There was no correlation between consumption of nondairy beverages with disease severity or QoL, but frequency of soft drink consumption correlated with SBP. With these results being supported by a literature review, it is reasonable to advise parents that fresh milk can be consumed by unsensitized children with AE. Soft drinks and other beverages should not be consumed in excess for optimal cardiovascular health and for other health reasons.

Patient acceptability, efficacy, and skin biophysiology of a cream and cleanser containing lipid complex with shea butter extract versus a ceramide product for eczema.

OBJECTIVES: To investigate patient acceptability, efficacy, and skin biophysiological effects of a cream/cleanser combination for childhood atopic dermatitis. SETTING: Paediatric dermatology clinic at a university teaching hospital in Hong Kong. PATIENTS: Consecutive paediatric patients with atopic dermatitis who were interested in trying a new moisturiser were recruited between 1 April 2013 and 31 March 2014. Swabs and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORing Atopic Dermatitis index), skin hydration, and transepidermal water loss were obtained prior to and following 4-week usage of a cream/cleanser containing lipid complex with shea butter extract (Ezerra cream; Hoe Pharma, Petaling Jaya, Malaysia). Global or general acceptability of treatment was documented as 'very good', 'good', 'fair', or 'poor'. RESULTS: A total of 34 patients with atopic dermatitis were recruited; 74% reported 'very good' or 'good', whereas 26% reported 'fair' or 'poor' general acceptability of treatment of the Ezerra cream; and 76% reported 'very good' or 'good', whereas 24% reported 'fair' or 'poor' general acceptability of treatment of the Ezerra cleanser. There were no intergroup differences in pre-usage clinical parameters of age, objective SCORing Atopic Dermatitis index, pruritus, sleep loss, skin hydration, transepidermal water loss, topical corticosteroid usage, oral antihistamine usage, or general acceptability of treatment of the prior emollient. Following use of the Ezerra cream, mean pruritus score decreased from 6.7 to 6.0 (P=0.036) and mean Children's Dermatology Life Quality Index improved from 10.0 to 8.0 (P=0.021) in the 'very good'/'good' group. There were no statistically significant differences in the acceptability of wash (P=0.526) and emollients (P=0.537) with pre-trial products. When compared with the data of another ceramide-precursor moisturiser in a previous study, there was no statistical difference in efficacy and acceptability between the two products. CONCLUSIONS: The trial cream was acceptable in three quarters of patients with atopic dermatitis. Patients who accepted the cream had less pruritus and improved quality of life than the non-accepting patients following its usage. The cream containing shea butter extract did not differ in acceptability or efficacy from a ceramide-precursor product. Patient acceptability is an important factor for treatment efficacy. There is a general lack of published clinical trials to document the efficacy and skin biophysiological effects of many of the proprietary moisturisers.

A generalized algorithm for the automatic diagnosis of sleep apnea from per-sample encoding of airflow and oximetry.

Objective. Sleep apnea is a common sleep breathing disorder that can significantly decrease sleep quality and have major health consequences. It is diagnosed based on the apnea hypopnea index (AHI). This study explored a novel, generalized algorithm for the automatic diagnosis of sleep apnea employing airflow (AF) and oximetry (SpO2) signals.Approach. Of the 988 polysomnography records, 45 were randomly selected for developing the automatic algorithm and the remainder 943 for validating purposes. The algorithm detects apnea events by a per-sample encoding process applied to the peak excursion of AF signal. Hypopnea events were detected from the per-sample encoding of AF and SpO2with an adjustment to time lag in SpO2. Total recording time was automatically processed and optimized for computation of total sleep time (TST). Total number of detected events and computed TST were used to estimate AHI. The estimated AHI was validated against the scored data from the Sleep Heart Health Study.Main results. Intraclass correlation coefficient of 0.94 was obtained between estimated and scored AHIs. The diagnostic accuracies were 93.5%, 92.4%, and 96.6% for AHI cut-off values of ≥5, ≥15, and ≥30 respectively. The overall accuracy for the combined severity categories (normal, mild, moderate, and severe) and kappa were 83.4% and 0.77 respectively.Significance. This new automatic technique was found to be superior to the other existing methods and can be applied to any portable sleep devices especially for home sleep apnea tests.

A novel algorithm for automatic diagnosis of sleep apnea from airflow and oximetry signals.

OBJECTIVE: Sleep apnea significantly decreases the quality of life. The apnea hypopnea index (AHI) is the main indicator for sleep apnea diagnosis. This study explored a novel automatic algorithm to diagnose sleep apnea from nasal airflow (AF) and pulse oximetry (SpO2) signals. APPROACH: Of the 988 polysomnography (PSG) records from the sleep heart health study (SHHS), 45 were randomly selected for the development of an algorithm and the remainder for validation (n = 943). The algorithm detects apnea events by a digitization process, following the determination of the peak excursion (peak-to-trough amplitude) from AF envelope. Hypopnea events were determined from the AF envelope and oxygen desaturation with correction to time lag in SpO2. Total sleep time (TST) was estimated from an optimized percentage of artefact-free total recording time. AHI was estimated from the number of detected events divided by the estimated TST. The estimated AHI was compared to the scored SHHS data for performance evaluation. MAIN RESULTS: The validation showed good agreement between the estimated and scored AHI (intraclass correlation coefficient of 0.95 and mean ±95% limits of agreement of -1.6 ±12.5 events h-1). The diagnostic accuracies were found: 90.7%, 91%, and 96.7% for AHI cut-off ≥5, ≥15, and ≥30 respectively. SIGNIFICANCE: The new algorithm is accurate over other existing methods for the automatic diagnosis of sleep apnea. It is applicable to any portable sleep screeners especially for the home diagnosis of sleep apnea.

Does age or gender influence quality of life in children with atopic dermatitis?

BACKGROUND: Quality of life (QoL) is impaired in children with atopic dermatitis (AD) but the various aspects of QoL may not be equally affected. Aim. To evaluate if age and gender affect some aspects of QoL in children with AD. METHOD: The Children's Dermatology Life Quality Index (CDLQI) was used for all children with AD seen at a paediatric dermatology clinic over a 3-year period. Disease severity was assessed using the SCORing Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS) tools. RESULTS: We reviewed CDLQI in 133 children (70 male and 63 female; age range 5-16 years) with AD. Itch, sleep disturbance, treatment and swimming/sports were the four aspects of QoL issues that were most commonly affected, in 50%, 47%, 38% and 29% of patients, respectively. Problems with interpersonal issues (friendship, school/holidays, and teasing/bullying) occurred in only a minority of children (

Classification methods to detect sleep apnea in adults based on respiratory and oximetry signals: a systematic review.

OBJECTIVE: Sleep apnea (SA), a common sleep disorder, can significantly decrease the quality of life, and is closely associated with major health risks such as cardiovascular disease, sudden death, depression, and hypertension. The normal diagnostic process of SA using polysomnography is costly and time consuming. In addition, the accuracy of different classification methods to detect SA varies with the use of different physiological signals. If an effective, reliable, and accurate classification method is developed, then the diagnosis of SA and its associated treatment will be time-efficient and economical. This study aims to systematically review the literature and present an overview of classification methods to detect SA using respiratory and oximetry signals and address the automated detection approach. APPROACH: Sixty-two included studies revealed the application of single and multiple signals (respiratory and oximetry) for the diagnosis of SA. MAIN RESULTS: Both airflow and oxygen saturation signals alone were effective in detecting SA in the case of binary decision-making, whereas multiple signals were good for multi-class detection. In addition, some machine learning methods were superior to the other classification methods for SA detection using respiratory and oximetry signals. SIGNIFICANCE: To deal with the respiratory and oximetry signals, a good choice of classification method as well as the consideration of associated factors would result in high accuracy in the detection of SA. An accurate classification method should provide a high detection rate with an automated (independent of human action) analysis of respiratory and oximetry signals. Future high-quality automated studies using large samples of data from multiple patient groups or record batches are recommended.

Regulation of the nuclear genes encoding the cytoplasmic and mitochondrial leucyl-tRNA synthetases of Neurospora crassa.

We show that the nuclear genes for the cytoplasmic and mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa are distinct in their encoded proteins, codon usage, mRNA levels, and regulation. The 4.2-kilobase-pair region representing the structural gene for cytoplasmic LeuRS and flanking regions has been sequenced. The positions of the 5' and 3' ends of mRNA and of a single 62-base-pair intron have been mapped. The methionine-initiated open reading frame encoded a protein of 1,123 amino acids and displayed a strong codon bias. Although cytoplasmic LeuRS shares with mitochondrial LeuRS some general features common to most aminoacyl-tRNA synthetases, there is little amino acid sequence similarity between them, mRNA levels for cytoplasmic LeuRS were much higher than those for mitochondrial LeuRS. This observation and the strong codon bias in the cytoplasmic LeuRS gene may contribute to a greater abundance of cytoplasmic LeuRS than mitochondrial LeuRS. The genes for cytoplasmic and mitochondrial LeuRS are regulated independently. The cytoplasmic LeuRS gene is regulated by the cross-pathway control system in N. crassa, which is analogous to general amino acid control in Saccharomyces cerevisiae. The cytoplasmic LeuRS mRNA levels are induced by amino acid starvation resulting from the addition of aminotriazole. Part of this increase is due to utilization of new transcription start sites. In contrast, the mitochondrial LeuRS gene is not induced by amino acid limitation. However, the mitochondrial LeuRS mRNA levels did increase dramatically upon inhibition of mitochondrial protein synthesis by chloramphenicol or ethidium bromide or in the temperature-sensitive strain leu-5 carrying a mutation in the mitochondrial LeuRS structural gene.

Nuclear gene for mitochondrial leucyl-tRNA synthetase of Neurospora crassa: isolation, sequence, chromosomal mapping, and evidence that the leu-5 locus specifies structural information.

We have isolated and characterized the nuclear gene for the mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa and have established that a defect in this structural gene is responsible for the leu-5 phenotype. We have purified mitochondrial LeuRS protein, determined its N-terminal sequence, and used this sequence information to identify and isolate a full-length genomic DNA clone. The 3.7-kilobase-pair region representing the structural gene and flanking regions has been sequenced. The 5' ends of the mRNA were mapped by S1 nuclease protection, and the 3' ends were determined from the sequence of cDNA clones. The gene contains a single short intron, 60 base pairs long. The methionine-initiated open reading frame specifies a 52-amino-acid mitochondrial targeting sequence followed by a 942-amino-acid protein. Restriction fragment length polymorphism analyses mapped the mitochondrial LeuRS structural gene to linkage group V, exactly where the leu-5 mutation had been mapped before. We show that the leu-5 strain has a defect in the structural gene for mitochondrial LeuRS by restoring growth under restrictive conditions for this strain after transformation with a wild-type copy of the mitochondrial LeuRS gene. We have cloned the mutant allele present in the leu-5 strain and identified the defect as being due to a Thr-to-Pro change in mitochondrial LeuRS. Finally, we have used immunoblotting to show that despite the apparent lack of mitochondrial LeuRS activity in leu-5 extracts, the leu-5 strain contains levels of mitochondrial LeuRS protein to similar to those of the wild-type strain.

Conservation of heterochromatin protein 1 function.

Heterochromatin represents a cytologically visible state of heritable gene repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to heterochromatin domains, including the centromeres, telomeres, and the donor mating-type loci, and is involved in silencing at these loci. We identify here the functional domains of swi6p and demonstrate that the chromodomain from a mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing that chromodomain function is conserved from yeasts to humans. Site-directed mutagenesis, based on a modeled three-dimensional structure of the swi6p chromodomain, shows that the hydrophobic amino acids which lie in the core of the structure are critical for biological function. Gel filtration, gel overlay experiments, and mass spectroscopy show that HP1 proteins can self-associate, and we suggest that it is as oligomers that HP1 proteins are incorporated into heterochromatin complexes that silence gene activity.

Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo-controlled cross-over trial.

BACKGROUND: Staphylococcus aureus (S. aureus) colonization/infection is an important factor in the pathophysiology of atopic dermatitis (AD). Clinical trials have demonstrated conflicting efficacy of diluted bleach baths in treating moderate-to-severe AD. We conducted a double-blinded, placebo-controlled (water), cross-over trial among patients with AD to investigate the efficacy of bleach baths in reducing S. aureus colonization and AD severity. METHOD: In this cross-over trial, 40 patients with moderate-to-severe AD were randomized to receive twice-weekly bleach and water baths, each for four consecutive weeks with a four-week wash-out period in between. Condition of S. aureus growth and SCORing Atopic Dermatitis index (SCORAD) were recorded at baseline and four-weekly intervals. Patients' blood was collected in first and second visits to investigate blood eosinophil count, serum levels of total IgE and specific IgEs against Staphylococcal enterotoxins A and B. In every visit, Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL) and usage frequency of prohibited medications (topical antibiotic, steroid and oral antihistamine) were recorded. RESULTS: All 40 patients completed the trial, but 14 were non-adherent. By intention-to-treat (ITT) approach, comparing with water baths, bleach baths conferred no significant efficacy in CDLQI, SH, TEWL, blood eosinophil count, total IgE and the two specific IgEs over four weeks. Water baths caused a greater reduction in affected area of SCORAD than bleach baths (-5.7 ± 15.4 for water vs. 0.6 ± 12.4 for bleach; p = 0.03) by ITT, and in objective SCORAD and affected area (p < 0.05) from per-protocol approach. Bleach baths reduced topical corticosteroid use (mean difference = 1.1 ± 2.6 days/week; p = 0.014) and topical antibiotic use (mean difference = 1.0 ± 2.8 days/week; p = 0.044) in within-group analysis. CONCLUSIONS: This study demonstrated that a four-week, twice-weekly regime of diluted bleach baths is not more useful than water baths in reducing S. aureus colonization/infection and improving AD. A longer treatment period is needed to evaluate if the short treatment duration was the main cause for the discrepancy in outcome from other bleach-bath trials. The usage of a portable bath tub obviates the problems associated with unavailability of bathing facilities in some families.

Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement.

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.

Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

Transmitral Doppler: a new transthoracic contrast method for patent foramen ovale detection and quantification.

OBJECTIVES: This study compared a new transthoracic echocardiographic (TTE) method for detection of right to left bubble passage, transmitral Doppler (TMD), against two-dimensional (2D) TTE contrast study and the gold standard, of transesophageal echocardiography (TEE), and assessed its utility in quantitative assessment of patent foramen ovales (PFO). BACKGROUND: Current TTE methods are relatively insensitive in PFO detection and do not allow quantitative assessment of right to left shunt. METHODS: In 44 patients (59 years, range 34 to 76 years) saline contrast and color Doppler studies were performed in three conditions--TTE TMD, TTE 2D and TEE. Bubble transit on the TMD was measured semiquantitatively by a visual bubble score and objectively by integrating the acoustic power within the mitral velocity envelope. RESULTS: By TEE it was determined that 17 patients (39%) had PFOs; 16 had right to left contrast passage, and only 1 had left to right flow by color Doppler. Against TEE contrast study, the sensitivity of TMD and 2D contrast studies were 100% and 75%, respectively, with specificity of 96% and 100%. Greater than 10 bubbles on a single beat of the resting contrast TMD identified patients with a maximum resting TEE PFO opening diameter >2 mm with 78% sensitivity and 100% specificity. There was a strong correlation (r2 = 0.72, p<0.01) between the TMD acoustic power and PFO opening diameter. CONCLUSIONS: Transmitral Doppler is a sensitive and specific method for TTE PFO detection that allows quantification of right to left bubble passage and may obviate the need for TEE in many patients after stroke.

Cytoplasmic leucyl-tRNA synthetase of Neurospora crassa is not specified by the leu-5 locus.

We generated a lambda gt11 Neurospora crassa cDNA library and screened the library for the cytoplasmic leucyl-tRNA synthetase (cyto LeuRS) clones using cyto LeuRS specific antibody. Two clones, lambda NCLRSC1 and lambda NCLRSC2, were obtained which have inserts of approximately 2 kbp and approximately 1.3 kbp, and which overlap by about 0.6 kbp. The following lines of evidence indicate that lambda NCLRSC1 and lambda NCLRSC2 encode parts of cyto LeuRS. (1) Antibodies affinity purified using either of the fusion proteins encoded by lambda NCLRSC1 or lambda NCLRSC2 inhibit cyto LeuRS activity. Thus, the fusion protein and cyto LeuRS share immunological determinants. (2) The same antibodies also react with an approximately 115-kDa protein, which comigrates with purified cyto LeuRS, in immunoblots of total N. crassa proteins. We used the cDNA clones to probe a N. crassa genomic DNA library and isolated two genomic DNA clones. Partial sequence analysis of cDNA and genomic DNA clones shows a methionine initiated open reading frame, which includes a stretch of amino acid residues that are highly conserved and that are at the ATP binding site in aminoacyl-tRNA synthetases. Using the cloned DNA as probe, we show that the cyto LeuRS mRNA is approximately 3900 nucleotides long. Finally, we have used restriction fragment length polymorphism mapping to show that the cyto LeuRS gene resides on the far right of linkage group II and not on linkage group V where the leu-5 mutation, which was previously reported to specify cyto LeuRS, is located.

Sleep in athletes undertaking protocols of exposure to nocturnal simulated altitude at 2650 m.

A popular method to attempt to enhance performance is for athletes to sleep at natural or simulated moderate altitude (SMA) when training daily near sea level. Based on our previous observation of periodic breathing in athletes sleeping at SMA, we hypothesised that athletes' sleep quality would also suffer with hypoxia. Using two typical protocols of nocturnal SMA (2650 m), we examined the effect on the sleep physiology of 14 male endurance-trained athletes. The selected protocols were Consecutive (15 successive exposure nights) and Intermittent (3x 5 successive exposure nights, interspersed with 2 normoxic nights) and athletes were randomly assigned to follow either one. We monitored sleep for two successive nights under baseline conditions (B; normoxia, 600 m) and then at weekly intervals (nights 1, 8 and 15 (N1, N8 and N15, respectively)) of the protocols. Since there was no significant difference in response between the protocols being followed (based on n=7, for each group) we are unable to support a preference for either one, although the likelihood of a Type II error must be acknowledged. For all athletes (n=14), respiratory disturbance and arousal responses between B and N1, although large in magnitude, were highly individual and not statistically significant. However, SpO2 decreased at N1 versus B (p<0.001) and remained lower on N8 (p<0.001) and N15 (p<0.001), not returning to baseline level. Compared to B, arousals were more frequent on N8 (p=0.02) and N15 (p=0.01). The percent of rapid eye movement sleep (REM) increased from N1 to N8 (p=0.03) and N15 (p=0.01). Overall, sleeping at 2650 m causes sleep disturbance in susceptible athletes, yet there was some improvement in REM sleep over the study duration.