Feasibility study of a parent-driven intervention for youth with Down syndrome.

BACKGROUND: Children with Down syndrome present with behavioural and emotional difficulties, including noncompliance, rule-breaking, emotion dysregulation and delays in executive functioning. Few behavioural interventions have been designed specifically for children with Down syndrome. The Research Units in Behavioral Intervention (RUBI) Parent Training for Disruptive Behaviors is a structured empirically supported parent training programme developed for caregivers of children with autism. This feasibility trial explored the feasibility and acceptability of an abbreviated RUBI intervention with caregivers of children with Down syndrome and identified promising outcome measures to target in future larger clinical trials. METHOD: A double-blind randomised feasibility pilot clinical trial allocated participants to a behavioural intervention (BEH) or educational (EDU) group. BEH and EDU consisted of five individual sessions over the course of 5 to 8 weeks. Measures were administered to 20 caregivers and their youth with Down syndrome at three time points. RESULTS: Both BEH and EDU were rated as feasible with high parental adherence and acceptable with high treatment satisfaction. Both BEH and EDU demonstrated decreased externalising behaviours, irritability and hyperactivity and improved behavioural regulation in executive functioning over time. No impact was noted on caregiver functioning. CONCLUSION: The feasibility trial has strong findings regarding feasibility and satisfaction and has promising findings regarding the selection of measures for future trials testing an adapted RUBI programme and an education programme to reduce behavioural challenges in children with Down syndrome. Larger scale clinical trials are needed to confirm promising findings of these feasible treatments.

Psychometric properties of inhibitory control measures among youth with Down syndrome.

BACKGROUND: Inhibitory control measures have been commonly used when assessing individuals with Down syndrome. However, minimal attention has been devoted to evaluating the appropriateness of specific assessments for use in this population, potentially leading to erroneous conclusions. This study aimed to examine the psychometric properties of measures of inhibitory control among youth with Down syndrome. We sought to examine the feasibility, presence of floor or practice effects, test-retest reliability, convergent validity and correlations with broader developmental domains of a set of inhibitory control tasks. METHODS: A sample of 97 youth with Down syndrome aged 6 to 17 years old participated in verbal and visuospatial tasks of inhibitory control including the Cat/dog Stroop, Neuropsychological Assessment Second Edition (NEPSY-II) Statue, National Institutes of Health (NIH) Toolbox Cognition Battery (TCB) Flanker, Leiter-3 Attention Sustained, and the Test of Attentional Performance for Children (KiTAP) Go/No-go and Distractibility subtests. Youth also completed standardised assessments of cognition and language, and caregivers completed rating scales. Psychometric properties on the tasks of inhibitory control were evaluated against a priori criteria. RESULTS: Apart from demonstrating negligible practice effects, adequate psychometric properties were not observed for any inhibitory control measure within the current sample's age range. One task with low working memory demands (NEPSY-II Statue) generally had better psychometric properties than the other tasks assessed. Subgroups of participants with an IQ greater than 30 and age more than 8 years were shown to be more likely to be able to complete the inhibition tasks. CONCLUSIONS: Findings suggest better feasibility for analogue tasks rather than computerised assessments of inhibitory control. Given the weak psychometrics of several common measures, future studies are required to evaluate other inhibitory control measures, specifically those with reduced working memory demands for youth with Down syndrome. Recommendations for use of the inhibitory control tasks among youth with Down syndrome are provided.

Survival and associated comorbidities in inclusion body myositis.

OBJECTIVE: To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. METHODS: We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. RESULTS: We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren's syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren's syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. CONCLUSIONS: IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren's syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.

Do Pulmonary Cavity Shapes Influence Lung Function?

Distribution of lung tissue within the chest cavity is a key contributor to delivery of both blood and air to the gas exchange regions of the lung. This distribution is multifactorial with influences from parenchyma, gravity, and level of inflation. We hypothesize that the manner in which lung inflates, for example, the primarily diaphragmatic nature of normal breathing, is an important contributor to regional lung tissue distribution. To investigate this hypothesis, we present an organ-level model of lung tissue mechanics, which incorporates pleural cavity change due to change in lung volume or posture. We quantify the changes using shape and density metrics in ten healthy subjects scanned supine at end-inspiratory and end-expiratory volumes and ten subjects scanned at both supine and prone end-inspiratory volumes. Comparing end-expiratory to end-inspiratory volume, we see primarily a change in the cranial-caudal dimension of the lung, reflective of movement of diaphragm. In the diaphragmatic region, there is greater regional lung expansion than in the cranial aspect, which is restricted by the chest wall. When moving from supine to prone, a restriction of lung was observed anteriorly, resulting in a generally reduced lung volume and a redistribution of air volume posteriorly. In general, we see the highest in lung tissue density heterogeneity in regions of the lung that are most inflated. Using our computational model, we quantify the impact of pleural cavity shape change on regional lung distribution and predict the impact on regional elastic recoil pressure.

Correction to: Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary.

The article Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary, written by Stanley A. Skinner, Elif Ilgaz Aydinlar, Lawrence F. Borges, Bob S. Carter, Bradford L. Currier, Vedran Deletis, Charles Dong, John Paul Dormans, Gea Drost, Isabel Fernandez­Conejero, E. Matthew Hoffman, Robert N. Holdefer, Paulo Andre Teixeira Kimaid, Antoun Koht, Karl F. Kothbauer, David B. MacDonald, John J. McAuliffe III, David E. Morledge, Susan H. Morris, Jonathan Norton, Klaus Novak, Kyung Seok Park, Joseph H. Perra, Julian Prell, David M. Rippe, Francesco Sala, Daniel M. Schwartz, Martín J. Segura, Kathleen Seidel, Christoph Seubert, Mirela V. Simon, Francisco Soto, Jeffrey A. Strommen, Andrea Szelenyi, Armando Tello, Sedat Ulkatan, Javier Urriza and Marshall Wilkinson, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 January 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 30 January 2019 to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort.

OBJECTIVE: To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. METHODS: Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for all subjects. RESULTS: A total of 509 individuals with incident exposure to an inclusive list of neurotoxic chemotherapy agents between 2006 and 2008 were identified. 268 (52.7%) of these individuals were determined to have CIPN. The median time from incident exposure to first documented symptoms was 71 days. Patients with CIPN received a neuropathy ICD-9 diagnosis in only 37 instances (13.8%). Pain symptoms and use of pain medications were observed more often in patients with CIPN. Five-year survival was greater in those with CIPN (55.2%) versus those without (36.1%). Those with CIPN surviving greater than 5 years (n=145) continued to have substantial impairments and were more likely to be prescribed opioids than those without CIPN (OR 2.0, 1.06-3.69). CONCLUSIONS: Results from our population-based study are consistent with previous reports of high incidence of CIPN in the first 2 years following incident exposure to neurotoxic chemotherapeutic agents, and its association with significant pain symptomatology and accompanied long-term opioid use. Increased survival following exposure to neurotoxic chemotherapy and its long-term disease burden necessitates further study among survivors.

In-flight characterization of the lunar orbiter laser altimeter instrument pointing and far-field pattern.

The Lunar Orbiter Laser Altimeter (LOLA) aboard the Lunar Reconnaissance Orbiter (LRO) has collected nearly seven billion measurements of surface height on the Moon with an absolute accuracy of ∼1 m and a precision of ∼10 cm. Converting time-of-flight laser altimeter measurements to topographic elevations requires accurate knowledge of the laser pointing with respect to the spacecraft body-fixed coordinate system. To that end, we have utilized altimetric crossovers from LOLA, as well as bidirectional observations of the LOLA laser and receiver boresight via an Earth-based laser tracking ground station. Based on a sample of ∼780,000 globally distributed crossovers from the circular-orbit phase of LRO's mission (∼27 months), we derive corrections to the LOLA laser boresight. These corrections improve the cross-track and along-track agreement of the crossovers by 24% and 33%, respectively, yielding RMS residuals of ∼10 m. Since early in the LRO mission, the bidirectional laser tracking experiments have confirmed a pointing anomaly when the LOLA instrument is facing toward deep space or the night side of the Moon and have allowed the reconstruction of the laser far-field pattern and receiver telescope pointing. By conducting such experiments shortly after launch and nearly eight years later, we have directly measured changes in the laser characteristics and obtained critical data to understand the laser behavior and refine the instrument pointing model. The methods and results presented here are also relevant to the design, fabrication, and operation of future planetary laser altimeters and their long-term behavior in the space environment.

Impact of sleep on executive functioning in school-age children with Down syndrome.

BACKGROUND: Sleep problems have an impact on executive functioning in the general population. While children with Down syndrome (DS) are at high risk for sleep problems, the impact of these sleep problems on executive functioning in school-age children with DS is less well documented. Our study examined the relationship between parent-reported and actigraphy-measured sleep duration and sleep quality with parent and teacher reports and neuropsychology assessments of executive functioning among school-age children with DS. METHOD: Thirty school-age children with DS wore an actigraph watch for a week at home at night. Their parent completed ratings of the child's sleep during that same week. Children completed a neuropsychology assessment of their inhibitory control, ability to shift and working memory. Their parents and teachers completed rating scales to assess these same constructs of executive functioning. RESULTS: Parent reports of restless sleep behaviours on the Children's Sleep Habits Questionnaire (CSHQ), but not actigraph-measured sleep period or efficiency, were predictive of parent reports of concerns with inhibitory control, shifting and working memory, and of teacher reports of inhibitory control. No measure of sleep was predictive of executive functioning as measured by the neuropsychology assessment. CONCLUSION: The study findings corroborate the preliminary literature that parent-reported sleep problems are related to executive functioning in school-age children with DS, particularly in the area of inhibitory control across home and school. These findings have implications for understanding contributing factors to academic performance and school behaviour in school-age children with DS.

Convergent validity of actigraphy with polysomnography and parent reports when measuring sleep in children with Down syndrome.

BACKGROUND: There is a need for rigorous measures of sleep in children with Down syndrome as sleep is a substantial problem in this population and there are barriers to obtaining the gold standard polysomnography (PSG). PSG is cost-prohibitive when measuring treatment effects in some clinical trials, and children with Down syndrome may not cooperate with undergoing a PSG. Minimal information is available on the validity of alternative methods of assessing sleep in children with Down syndrome, such as actigraphy and parent ratings. Our study examined the concurrent and convergent validity of different measures of sleep, including PSG, actigraphy and parent reports of sleep among children with Down syndrome. METHOD: A clinic (n = 27) and a community (n = 47) sample of children with Down syndrome were examined. In clinic, children with Down syndrome wore an actigraph watch during a routine PSG. In the community, children with Down syndrome wore an actigraph watch for a week at home at night as part of a larger study on sleep and behaviour. Their parent completed ratings of the child's sleep during that same week. RESULTS: Actigraph watches demonstrated convergent validity with PSG when measuring a child with Down syndrome's total amount of sleep time, total wake time after sleep onset and sleep period efficiency. In contrast, actigraph watches demonstrated poor correlations with parent reports of sleep, and with PSG when measuring the total time in bed and total wake episodes. Actigraphy, PSG and parent ratings of sleep demonstrated poor concurrent validity with clinical diagnosis of obstructive sleep apnoea. CONCLUSION: Our current data suggest that actigraph watches demonstrate convergent validity and are sensitive to measuring certain sleep constructs (duration, efficiency) in children with Down syndrome. However, parent reports, such as the Children's Sleep Habits Questionnaire, may be measuring other sleep constructs. These findings highlight the importance of selecting measures of sleep related to target concerns.

Reliability of parent report measures of behaviour in children with Down syndrome.

BACKGROUND: Behavioural problems are common among children with Down syndrome (DS). Tools to detect and evaluate maladaptive behaviours have been developed for typically developing children and have been evaluated for use among children with intellectual and developmental disabilities. However, these measures have not been evaluated for use specifically in children with DS. This psychometric evaluation is important given that some clinically observed behaviours are not addressed in currently available rating scales. The current study evaluates the psychometric properties of the Child Behavior Checklist (CBCL), a commonly used screening tool developed for typically developing children and commonly used with children with intellectual and developmental disabilities. METHODS: The study investigated the psychometric properties of the CBCL among school-aged children with DS, including an assessment of the rate of detecting behaviour problems, concerns with distribution, internal consistency, inter-rater reliability and convergent and discriminant validity with the Aberrant Behavior Checklist and Nisonger Child Behavior Rating Form. Caregivers of 88 children with DS aged 6-18 years rated their child's behaviour with the CBCL, Aberrant Behavior Checklist and Nisonger Child Behavior Rating Form. Teachers completed the Teacher Report Form. RESULTS: About one-third of children with DS were reported to exhibit behaviours of clinical concern on the total score of the CBCL. Internal consistency for CBCL sub-scales was poor to excellent, and inter-rater reliability was generally acceptable. The sub-scales of the CBCL performed best when evaluating convergent validity, with variable discriminant validity. Normative data conversions controlled for age and gender differences in this sample. CONCLUSIONS: The study findings suggest that, among children with DS, some CBCL sub-scales generally performed in a psychometrically sound and theoretically appropriate manner in relation to other measures of behaviour. Caution is warranted when interpreting specific sub-scales (Anxious/Depressed, Somatic Complaints and Thought Problems). The CBCL can continue to be used as a screening measure when evaluating behavioural concerns among children with DS, acknowledging poor discriminant validity and the possibility that key behaviour concerns in DS may not be captured by the CBCL screen.

Links between sleep and daytime behaviour problems in children with Down syndrome.

BACKGROUND: In the general population, sleep problems have an impact on daytime performance. Despite sleep problems being common among children with Down syndrome, the impact of sleep problems on daytime behaviours in school-age children with Down syndrome is an understudied topic. Our study examined the relationship between parent-reported and actigraphy-measured sleep duration and sleep quality with parent and teacher reports of daytime behaviour problems among school-age children with Down syndrome. METHOD: Thirty school-age children with Down syndrome wore an actigraph watch for a week at home at night. Their parent completed ratings of the child's sleep during that same week. Their parent and teacher completed a battery of measures to assess daytime behaviour. RESULTS: Parent reports of restless sleep behaviours on the Children's Sleep Habits Questionnaire, but not actigraph-measured sleep efficiency, was predictive of parent and teacher behavioural concerns on the Nisonger Child Behaviour Rating Form and the Vanderbilt ADHD Rating Scales. Actigraph-measured sleep period and parent-reported sleep duration on the Children's Sleep Habits Questionnaire was predictive of daytime parent-reported inattention. Actigraph-measured sleep period was predictive of parent-reported hyperactivity/impulsivity. CONCLUSION: The study findings suggest that sleep problems have complex relationships to both parent-reported and teacher-reported daytime behaviour concerns in children with Down syndrome. These findings have implications for understanding the factors impacting behavioural concerns and their treatment in school-age children with Down syndrome.

Reliability of parent report measures of sleep in children with Down syndrome.

BACKGROUND: Behavioural sleep disturbances are common among children with Down syndrome (DS). However, tools used to detect and evaluate behavioural sleep disturbances were developed for typically developing children and have not been evaluated for use among children with DS. The current study evaluates the psychometric properties of three measures of behavioural sleep disturbances that are currently being used with children with intellectual and developmental disabilities, including children with DS. METHOD: Caregivers of 30 children with DS rated their child's sleep with the Behavioral Evaluation of Disorders of Sleep (BEDS), Children's Sleep Habits Questionnaire (CSHQ) and Sleep Disturbances Scale for Children (SDSC). Caregivers also provided information on sleep diagnoses and completed a 7-night sleep and behaviour diary. RESULTS: The study investigated the rate of detecting sleep problems, internal consistency, and convergent and concurrent validity of the BEDS, CSHQ and SDSC. Children with DS were reported to exhibit behavioural sleep disturbances at different rates depending on the measure used; 0% BEDS, 79.3% CSHQ and 17.2% SDSC. Internal consistency was comparable for all three measures for their total scores. However, when evaluating the internal consistency of subscale scores, those on the CSHQ and SDSC performed more strongly. The subscales of the CSHQ performed best when evaluating convergent and concurrent validity, with the SDSC subscales performing moderately well. CONCLUSION: The study findings suggest that, among children with DS, the CSHQ and its subscales performed in a psychometrically sound and theoretically appropriate manner in relation to other measures of sleep, medical history of sleep problems, and daily reports of sleep and associated behaviours. The SDSC performed moderately well. When evaluating behavioural sleep disturbances among children with DS, the CSHQ is recommended based on its stronger psychometric properties.

French Osteotomy for Cubitus Varus in Children: A Long-term Study Over 27 Years.

BACKGROUND: Cubitus varus is a cosmetically unacceptable complication of supracondylar fractures of the elbow in children. We have performed the lateral closing wedge (French) osteotomy to correct the varus for 27 years. More complex osteotomies have been described to correct the associated hyperextension and internal rotation deformities and to prevent a prominent lateral condyle. METHODS: We retrospectively reviewed 90 consecutive patients (1986 to 2012). The mean age of the patients at surgery was 8.2 years (3 to 14 y). The varus angle (mean, 21.4 degrees; range, 8 to 40 degrees) was assessed preoperatively with the humero-elbow-wrist angle. The postoperative carrying angle (mean, 10.4 degrees) and the preoperative and postoperative range of movement were assessed clinically. The lateral condylar prominence index (LCPI) was retrospectively measured at union. RESULTS: Eighty-four (93.3%) of the patients had a good or excellent result. Six (6.7%) had a poor result (residual varus, loss of >20 degrees of preoperative range of flexion or extension or a complication necessitating resurgery). There were no neurovascular complications. The mean LCPI was +0.14. CONCLUSIONS: The results of the French osteotomy are comparable with the more technically demanding dome, step-cut translation, and multiplanar osteotomies, with a lower complication rate. The literature reports adequate remodeling of the hyperextension deformity (≤10 y) and the LCPI (≤12 y), and that the internal rotation deformity is well tolerated by the patient. LEVEL OF EVIDENCE: Level IV-case series.

Asthma and allergy development: contrasting influences of yeasts and other fungal exposures.

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Wheeze in infancy: protection associated with yeasts in house dust contrasts with increased risk associated with yeasts in indoor air and other fungal taxa.

BACKGROUND: While fungal exposures are assumed to provoke wheeze through irritant or allergenic mechanisms, little is known about the differential effects of indoor and outdoor fungi on early-life wheeze. METHODS: In a Boston prospective birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and outdoor air were measured at the age of 2-3 months. Wheeze was determined using bimonthly telephone questionnaires. Odds ratios were estimated for an interquartile increase in fungal natural log-transformed concentrations, adjusting for predictors of wheeze and potential confounders. RESULTS: Increased odds of 'any wheeze' (≥1 vs 0 episodes) by age one were positively associated with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR = 1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (≥2 vs <2 episodes) by age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was associated with any wheeze for children with maternal mold sensitization [OR = 9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR = 1.32; (0.79-2.20)]. CONCLUSIONS: While wheeze rates were higher with exposures to fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts in the home had a strong protective association with wheeze in infancy. Molecular microbiologic studies may elucidate specific components of innate microbiologic stimulants that lead to contrasting effects on wheeze development.

Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding.

We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or eradication of this condition.

Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.

The dystrophin associated proteins (DAPs) are good candidates for harboring primary mutations in the genetically heterogeneous autosomal recessive muscular dystrophies (ARMD). The transmembrane components of the DAPs can be separated into the dystroglycan and the sarcoglycan complexes. Here we report the isolation of cDNAs encoding the 43 kD sarcoglycan protein beta-sarcoglycan (A3b) and the localization of the human gene to chromosome 4q12. We describe a young girl with ARMD with truncating mutations on both alleles. Immunostaining of her muscle biopsy shows specific loss of the components of the sarcoglycan complex (beta-sarcoglycan, alpha-sarcoglycan (adhalin), and 35 kD sarcoglycan). Thus secondary destabilization of the sarcoglycan complex may be an important pathophysiological event in ARMD.

Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury.

The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD-deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.