Obesity, diabetes and their metabolic correlates in middle-aged adults with Down syndrome.

BACKGROUND: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. METHODS: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) and obese (BMI ≥ 30 kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. RESULTS: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). CONCLUSIONS: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.

Motivation and treatment credibility predict alliance in cognitive behavioral treatment for youth with anxiety disorders in community clinics.

OBJECTIVE: We examined whether motivation and treatment credibility predicted alliance in a 10-session cognitive behavioral treatment delivered in community clinics for youth anxiety disorders. METHOD: Ninety-one clinic-referred youths (meanage  = 11.4 years, standard deviation = 2.1, range 8-15 years, 49.5% boys) with anxiety disorders-rated treatment motivation at pretreatment and perceived treatment credibility after session 1. Youths and therapists (YT) rated alliance after session 3 (early) and session 7 (late). Hierarchical linear models were applied to examine whether motivation and treatment credibility predicted YT early alliance, YT alliance change, and YT alliance agreement. RESULTS: Motivation predicted high early YT alliance, but not YT alliance change or alliance agreement. Youth-rated treatment credibility predicted high early youth alliance and high YT positive alliance change, but not early therapist alliance or alliance agreement. CONCLUSION: Conclusion Efforts to enhance youth motivation and treatment credibility early in treatment could facilitate the formation of a strong YT alliance.

An improved method for detecting telomere size differences in T-lymphocyte interphases from older people with Down syndrome with and without mild cognitive impairment.

Telomere size (quantified by fluorescence intensity and physical lengths) in short-term T-lymphocyte cultures from adults with Down syndrome (DS) with and without mild cognitive impairment (MCI-DS) or dementia was compared. For these studies, dementia status was determined based on longitudinal assessments employing a battery of cognitive and functional assessments developed to distinguish adult-onset impairment from preexisting developmental disability. In the course of our studies using a MetaSystems Image Analyzer in combination with ISIS software and a Zeiss Axioskop 2, we found that Fluorescein isothiocyanate (FITC) telomere fluorescence referenced to chromosome 2-identified FITC probe fluorescence as a nontelomere standard (telomere/cen2 ratio) showed great promise as a biomarker of early decline associated with Alzheimer's disease (AD) in this high-risk population. We have now obtained a cen (2) CY3 probe that can clearly be distinguished from the blue-green FITC interphase telomere probe, providing a clear distinction between telomere and centromere fluorescence in both interphase and metaphase. We used FITC/CY3 light intensity ratios to compare telomere length in interphases in adults with DS with and without MCI-DS or dementia. Five age-matched female and five age-matched male pairs (n = 10) all showed clear evidence of telomere shortening associated with clinical progression of AD (P < 0.002 - P < 0.000001), with distributions of mean values for cases and controls showing no overlap. We also examined the time needed for microscopy using interphase versus metaphase fluorescence preparations. With interphase preparations, examination time was reduced by an order of magnitude compared with metaphase preparations, indicating that the methods employed herein have considerable practical promise for translation into broad diagnostic practice.

Anatomy of the cutaneous surface of the male genitalia, with elaboration upon the inner preputial coronal-shaft junction.

INTRODUCTION: Descriptions of the penile prepuce in anatomical and clinical texts either omit details or contain a small, yet potentially serious, error with regard to the manner of its attachment to the penis. OBJECTIVE: This study sought to cast light on a ubiquitous but poorly understood and under-appreciated structure, while correcting a long-standing mistake in the medical literature. STUDY DESIGN: The foreskins of five male stillborn babies were dissected and carefully examined. Tissue from the apposing surfaces of the various regions of the inner and outer prepuce surfaces and the transition zone itself were collected, embedded in paraffin, sectioned, stained, examined and photographed under microscopy. RESULTS: Contradicting the prevailing descriptions in the literature that the inner prepuce is a single, uniform sheath, this study's observations and histological findings demonstrated that it actually splits into separate laminae that connect distally to the shaft at the base of the corona and proximally with the shaft fascia, respectively (Figure). DISCUSSION: The penile prepuce is a discrete and deceptively complex part of the male anatomy, yet key details of its interposing surfaces are inaccurately described or entirely omitted in the literature. Understanding the normal anatomy of the prepuce is critically relevant, particularly for urologists and others involved in the performance of circumcision. For example, avoiding potentially catastrophic avulsion of the inner preputial remnant beyond the coronal sulcus during circumcision and accurate assessment of tissue positioning prior to penile reconstruction in cases of hypospadias. CONCLUSION: The findings of this study correct a misunderstanding in the anatomy of the prepuce.

Rapid assessment of cognitive function in down syndrome across intellectual level and dementia status.

BACKGROUND: Adults with Down syndrome (DS) are at risk of developing dementia and cognitive assessment is a fundamental part of the diagnostic process. Previously, we developed a Rapid Assessment for Developmental Disabilities (RADD), a brief, broadly focused direct test of cognition. In the current report, we assess whether the RADD is sensitive to dementia in DS and the degree to which it compares with other cognitive measures of dementia in this population. METHODS: In a sample of 114 individuals with DS, with dementia diagnosed in 62%, the RADD was compared with the Dementia Questionnaire for Mentally Retarded Persons (DMR), the Bristol Activities of Daily Living Scale, Severe Impairment Battery (SIB), and the Brief Praxis Test (BPT). RESULTS: The RADD showed predicted effects across intellectual disability (ID) levels and dementia status (p < 0.001). Six-month test-retest reliability for the subset of individuals without dementia was high (r(41) = 0.95, p < 0.001). Criterion-referenced validity was demonstrated by correlations between RADD scores and ID levels based upon prior intelligence testing and clinical diagnoses (rs (114) = 0.67, p = 0.001) and with other measures of cognitive skills, such as the BPT, SIB, and DMR-Sum of Cognitive scores (range 0.84 through 0.92). Using receiver operating characteristic curves for groups varying in pre-morbid severity of ID, the RADD exhibited high sensitivity (0.87) and specificity (0.81) in discriminating among individuals with and without dementia, although sensitivity was somewhat lower (0.73) for the subsample of dementia cases diagnosed no more than 2 years prior to their RADD assessment. CONCLUSION: Taken together, findings indicated that the RADD, a relatively brief, easy-to-administer test for cognitive function assessment across ID levels and dementia status, would be a useful component of cognitive assessments for adults with DS, including assessments explicitly focused on dementia.

Change in plasma Aß peptides and onset of dementia in adults with Down syndrome.

OBJECTIVE: To examine changes in levels of plasma amyloid-ß (Aß) peptides, Aß42 and Aß40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS). METHODS: Plasma Aß42 and Aß40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aß peptide change group (increasing, no change, or decreasing), adjusting for covariates. RESULTS: Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aß42 levels, a decrease in the Aß42/Aß40 ratio, and an increase in Aß40 levels were related to conversion to AD. Compared with the group with increasing levels of Aß42, the likelihood of developing AD was 5 times higher for those whose plasma Aß42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aß42/Aß40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aß40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9). CONCLUSIONS: Among adults with DS, decreasing levels of plasma Aß42, a decline in the Aß42/Aß40 ratio, or increasing levels of Aß40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aß peptides in the brain.

Dementia of the Alzheimer's type and accelerated aging in Down syndrome.

This case study, of a woman with Down syndrome and dementia of the Alzheimer's type (DAT), follows the course of her decline over an 11-year period until death at age 57. Detailed neuropathological findings are also presented. This case illustrates features of premature aging that are typically associated with Down syndrome, and the progressive changes in memory and cognition that are usually associated with DAT. Although the subject's cardiovascular condition and thyroid disorder were treated, they may have contributed to the decline of her memory. This case shows the difficulty in diagnosing dementia in an individual with mental retardation who suffered comorbid episodes of depression and psychosis.

Changes in explicit memory associated with early dementia in adults with Down's syndrome.

BACKGROUND: A modified version of the Selective Reminding Test (SRT) (Buschke 1973) was used to examine the changes in memory that occur with early-stage dementia of the Alzheimer's type (DAT) in adults with intellectual disability (ID) and Down's syndrome (DS), and to compare these changes to those occurring with 'normal' ageing. METHOD: Hierarchical linear modelling analyses showed steep declines in the performance of participants who had met the criteria for the onset of DAT. Non-demented participants also showed declines in performance which were related to their age. However, the absolute magnitude of these declines was consistent with a 'normal' ageing pattern and not with undetected dementia. RESULTS: In analysing the specific memory components that are compromised, the present authors found that participants with early-stage DAT showed severely diminished long-term storage and retrieval processing abilities compared to their non-demented peers. Notably, these declines preceded other symptoms of dementia, in most cases by more than a full year and sometimes by as much as 3 years. CONCLUSIONS: Thus, the present results clearly confirm that memory processes are affected during early dementia in adults with DS, and that the SRT has promise as a clinical tool.

An analysis of the RCMAS Lie scale in a clinic sample of anxious children.

Examined Revised Children's Manifest Anxiety Scale (RCMAS) Lie scores in a sample of 284 anxious children. Lie scores were examined in relation to children's age, ethnicity/race, and gender, and in relation to Total Anxiety scores. The utility of Lie scores also was examined in terms of whether they were predictive of children's anxiety levels as rated by children themselves, parents, and clinicians. Between-group differences in children's Lie scores were examined as well. Results indicated that younger children had significantly higher Lie scores than older children, and Hispanic American children had significantly higher Lie scores than European American children. There were no significant gender differences in Lie scores, and no significant relation was found between RCMAS Lie scores and Total Anxiety scores for the total sample. Subgroup analyses indicated that Lie scores were predictive of children's anxiety levels. Results also indicated that Lie scores were significantly different between children who presented with anxiety disorders and children who presented with anxiety and externalizing disorders. Findings are discussed in terms of the usefulness of RCMAS Lie scores.

Test-retest reliability of anxiety symptoms and diagnoses with the Anxiety Disorders Interview Schedule for DSM-IV: child and parent versions.

OBJECTIVE: To examine the test-retest reliability of the DSM-IV anxiety symptoms and disorders in children with the Anxiety Disorders Interview Schedule for DSM-IV: Child and Parent Versions (ADIS for DSM-IV:C/P). METHOD: Sixty-two children (aged 7-16 years) and their parents underwent two administrations of the ADIS for DSM-IV:C/P with a test-retest interval of 7 to 14 days. RESULTS AND CONCLUSIONS: Results revealed that the ADIS for DSM-IV:C/P is a reliable instrument for deriving DSM-IV anxiety disorder symptoms and diagnoses in children. The ADIS for DSM-IV:C/P was found to have excellent reliability in symptom scale scores for separation anxiety disorder, social phobia, specific phobia, and generalized anxiety disorder and good to excellent reliability for deriving combined diagnoses of these disorders, as well as using child-only and parent-only interview information. Reliability coefficients were generally similar and, in most instances, superior to those found in previous ADIS-C/P reliability studies. Limitations and directions for future research are discussed.

Hybrid classification of sphincter of Oddi dysfunction based on simplified Milwaukee criteria: effect of marginal serum liver and pancreas test elevations.

To date, when using the Milwaukee classification for sphincter of Oddi dysfunction (SOD), one cannot accurately classify patients with marginal elevations in laboratory tests; ie, < 1.5 x the upper limit of normal (ULN). Since subsequent treatment may depend on how they are classified, we sought to determine whether these patients should be considered as type II or type III. Between January 1993 and October 1996, 113 consecutive patients (82 females and 31 males; ages 12-87 years) without prior sphincterotomy were referred to consider a diagnosis of SOD type II or III. SOD II patients had pancreaticobiliary-type pain and laboratory elevations >1.5 x ULN or dilated ducts, while SOD III patients had pain only. Hybrid patients had pain and marginal laboratory elevations <1.5 x ULN, with normal duct diameters. Drainage times, frequency, duration, and propagation were not assessed. Sphincter of Oddi manometry (SOM) was performed in each case, and the frequency of abnormal biliary and/or pancreatic basal sphincter pressure was compared, with respect to type II, III, and hybrid SOD. Successful SOM was obtained in 113/114 patients: Abnormal basal sphincter pressure was found in 65, 89, and 43% of type II, hybrid, and type III SOD, respectively. We found no statistical difference between type II and hybrid patients. In contrast, there was statistical difference between types II and III patients and between type III and hybrid patients. In conclusion, there was no significant difference in the frequency of elevated basal sphincter pressure in SOD type II versus hybrid, and thus they should be considered as one group.

Representation and simulation of biochemical processes using the pi-calculus process algebra.

Despite the rapidly accumulating body of knowledge about protein networks, there is currently no convenient way of sharing and manipulation of such information. We suggest that a formal computer language for describing the biomolecular processes underlying protein networks is essential for rapid advancement in this field. We propose to model biomolecular processes by using the pi-Calculus, a process algebra, originally developed for describing computer processes. Our model for biochemical processes is mathematically well-defined, while remaining biologically faithful and transparent. It is amenable to computer simulation, analysis and formal verification. We have developed a computer simulation system, the PiFCP, for execution and analysis of pi-calculus programs. The system allows us to trace, debug and monitor the behavior of biochemical networks under various manipulations. We present a pi-calculus model for the RTK-MAPK signal transduction pathway, formally represent detailed molecular and biochemical information, and study it by various PiFCP simulations.