Keep it simple: comparing functional assessments in individuals with Down syndrome.

BACKGROUND: A number of assessments exist that evaluate function in ambulatory adults. However, these assessments take for granted the cognitive abilities required for the participant to understand what is being asked of them in order to demonstrate their functional abilities. It has been shown that individuals with Down syndrome (DS) demonstrate lower functional levels when asked to perform additional tasks while walking. Therefore, measurements of function may not be reflective of actual function if the assessment requires additional tasks in those with DS. It is for these reasons the current investigation sought to evaluate four common functional assessments, two with [modified Berg balance test (mBERG) and Functional Gait Assessment (FGA)] and two without [Timed Up and Go (TUG) and Established Populations for Epidemiologic Study in the Elderly (EPESE)] complex tasks. METHODS: Adults with DS (n = 19) completed four functional assessments, which were later compared using bivariate Pearson correlation coefficients. RESULTS: There were large associations between simple assessments (TUG-EPESE: r = -0.525, P = 0.021) and complex assessments (FGA-mBERG: r = 0.612, P = 0.005), respectively. The TUG also inversely correlated with the FGA (r = -0.476, P = 0.039), and the EPESE had a large association with mBERG (r = 0.508, P = 0.027). CONCLUSIONS: The mBERG may be the best test to replicate real-world scenarios through its tasks, although it may also be confounded by the cognitive load required to perform the movements as asked. The TUG and EPESE may be more appropriate as mobility assessments because they require very little cognitive attention when completing the tasks. True assessments of mobility ought to err on the side of simple so to not confuse the outcomes with executive functionality.

Field-based versus laboratory-based estimates of muscle quality index in adolescents with and without Down syndrome.

BACKGROUND: Low muscle quality index (MQI) is a potential risk of developing functional impairments in older people. However, considering that individuals with Down syndrome (DS) present with a faster decline in biological aging, an investigation on MQI in individuals with DS is necessary. The aims of this present cross-sectional study were to compare (1) MQI between adolescents with and without DS and (2) evaluate laboratory versus field-based estimates of MQI. METHODS: Fifty-six adolescents were recruited and separated into two groups: DS (n = 30, 13 boys and 17 girls; age: 12.38 ± 3.07 years) and a control (non-DS; n = 26, 9 boys and 17 girls; age: 12.46 ± 2.88 years). Laboratory MQI was derived from the ratio of grip strength to arm muscle mass (in kg) measured by dual-energy X-ray absorptiometry (DXA). Field-based MQI was quantified from the ratio of hand grip strength (HGS) to body mass index (BMI). For statistical analyses, a two-way ANOVA was conducted for group comparisons, and a Pearson correlation was used to test the association between field MQI and laboratory MQI. RESULTS: Adolescents with DS displayed lower field (P = 0.001), laboratory MQI estimates (P = 0.001) and HGS (P = 0.001) as compared non-DS. Also, there was a strong correlation effect between field MQI and laboratory MQI estimates (P < 0.001, R = 0.81). CONCLUSION: Adolescents with DS have lower field and laboratory MQI compared with adolescents without DS. Simpler field MQI might be used in daily clinical practice, with special attention to those with DS.

Childhood trauma and cognitive functioning in individuals at clinical high risk (CHR) for psychosis.

Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.

Correction to: Anticoagulant Rodenticides and Raptors: Recent Findings from New York, 1998-2001.

In the original version of this article, there is a typographical error in the third sentence of the Results and Discussion section. The number of cases in which anticoagulant-facilitated hemorrhage was considered the cause of death was 19 (not 9). This has been corrected with this erratum.

Consonant differentiation mediates the discrepancy between non-verbal and verbal abilities in children with ASD.

BACKGROUND: Many children with autism spectrum disorder (ASD) demonstrate verbal communication disorders reflected in lower verbal than non-verbal abilities. The present study examined the extent to which this discrepancy is associated with atypical speech sound differentiation. METHODS: Differences in the amplitude of auditory event-related potentials elicited by contrasting consonant-vowel syllables during a passive listening paradigm were used to assess speech sound differentiation in 24 children with ASD and 18 chronological age-matched children with typical development (TD), M age 6.90 years (SD = 1.39). RESULTS: Results revealed that compared with TD peers, children with ASD showed reduced consonant differentiation in the 84- to 308-ms period. Brain responses indexing consonant differentiation were negatively related to the degree of discrepancy in non-verbal and verbal abilities and mediated the relationship between diagnostic group membership and the greater discrepancy. CONCLUSIONS: We discuss the theoretical and clinical implications of the brain's response to speech sound contrasts possibly explaining the greater non-verbal versus language ability in children with ASD compared with that in typically developing children.

Influence of infection on malaria-specific antibody dynamics in a cohort exposed to intense malaria transmission in northern Uganda.

The role of submicroscopic infections in modulating malaria antibody responses is poorly understood and requires longitudinal studies. A cohort of 249 children ≤5 years of age, 126 children between 6 and 10 years and 134 adults ≥20 years was recruited in an area of intense malaria transmission in Apac, Uganda and treated with artemether/lumefantrine at enrolment. Parasite carriage was determined at enrolment and after 6 and 16 weeks using microscopy and PCR. Antibody prevalence and titres to circumsporozoite protein, apical membrane antigen-1 (AMA-1), merozoite surface protein-1 (MSP-119 ), merozoite surface protein-2 (MSP-2) and Anopheles gambiae salivary gland protein 6 (gSG6) were determined by ELISA. Plasmodium falciparum infections were detected in 38·1% (194/509) of the individuals by microscopy and in 57·1% (284/493) of the individuals by PCR at enrolment. Antibody prevalence and titre against AMA-1, MSP-119 , MSP-2 and gSG6 were related to concurrent (sub-)microscopic parasitaemia. Responses were stable in children who were continuously infected with malaria parasites but declined in children who were never parasitaemic during the study or were not re-infected after treatment. These findings indicate that continued malaria infections are required to maintain antibody titres in an area of intense malaria transmission.

Brown midrib corn silage fed during the peripartal period increased intake and resulted in a persistent increase in milk solids yield of Holstein cows.

The objective of this study was to evaluate transition cow performance when brown midrib corn silage (BMRCS; Mycogen F2F444) was included in the diet during the transition period, and to determine if any production response occurring during the first 3 wk of lactation would persist from wk 4 to 15 when a common diet was fed. Seventy Holstein dairy cows were blocked by parity (either second or third and greater) and calving date and randomly assigned to the CCS (a mixture of varieties of conventional corn silage) or BMRCS treatment. Diets were formulated with the objective of keeping all ration parameters the same, with the exception of neutral detergent fiber digestibility. Neutral detergent fiber digestibility values (30 h) for CCS and BMRCS averaged 56.8 and 73.8%, respectively. Prepartum rations contained 47% corn silage, 18% wheat straw, 7% alfalfa haylage, and 28% concentrate, and averaged 45% neutral detergent fiber (DM basis). Postpartum rations contained 40% corn silage, 15% alfalfa haylage, 1% straw, and 44% concentrate. Milk weights (3×/d) and dry matter intake were recorded daily, and milk composition was measured weekly. Cows fed BMRCS had higher dry matter intake during the 2-wk period before calving (14.3 vs. 13.2 kg/d) and the 3-wk period after calving (20.1 vs. 18.1 kg/d) than did cows fed CCS. Yields of milk, solids, and lactose were increased, whereas a trend was observed for a reduction in somatic cell counts and linear scores in the postpartum period for cows receiving BMRCS during the transition. A significant carryover effect of BMRCS was observed on production from wk 4 to 15 when the common diet was fed, with yields of protein (1.36 vs. 1.30 kg/d), lactose (2.24 vs. 2.12 kg/d), and solids (5.82 vs. 5.51 kg/d) increasing significantly, and yields of fat-corrected milk, energy-corrected milk, and fat tending to increase during this period for cows that had been fed BMRCS. The increased intakes during the last 2 wk of the prepartum period in the BMRCS treatment were likely because of a reduction in fill, whereas the increased intakes in the postpartum period in cows fed the BMRCS were either because of the higher intakes during the prepartum period or because of a reduction in fill limitations in the postpartum period. The carryover response in wk 4 to 15 may have resulted from cows that received BMRCS during the transition period being in a more positive nutrient balance than cows fed CCS. The results of this study indicate the importance that digestible NDF can have in transition diets and the long-term production responses that can occur when intake is increased in the transition period.

Muscle Quality Is Associated with History of Falls in Octogenarians.

OBJECTIVES: The aim of this study was to compare muscle quality (MQ) between octogenarians classified as non-fallers, fallers and recurrent fallers and identify confounding intrinsic and extrensic factors that impact likelihood for falls. DESIGN: This observational, descriptive, cross-sectional study included older adults (N=220) aged 80 years or older. MEASUREMENTS: The Short Physical Performance Battery (SPPB) was used to evaluate physical function and MQ was calculated using the ratio of grip strength to arm muscle mass (in kilograms) quantified by DXA. Variables related to sociodemographic, clinical, cognitive function, and falls were evaluated using a questionnaire and symptoms of depression were evaluated by the Geriatric Depression Scale (GDS). A Kruskal-Wallis H test was used to verify differences between groups. Binomial logistic regression was performed to determine the impact of age, depression, polypharmacy, balance, MQ, and sex on participants having more than four falls in their history. RESULTS: Increasing MQ was associated with reduced likelihood of more than four falls in their history. Non-fallers were statistically younger (p = 0.012) and took more medications (p = 0.023) than recurrent fallers. Recurrent fallers had lower MQ when compared with fallers (p = 0.007) and non-fallers (p = 0.001) and had a lower GDS score when compared with fallers (p = 0.022). Finally, fallers presented lower scores for balance when compared to non-fallers (p = 0.013). CONCLUSION: A higher MQ is associated with a reduction in the likelihood falls in octogenarians. Therefore, it may be advantageous for clinicians to evaluate MQ when the screening of the risk of falls in older adults.

Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease that culminates in cirrhosis. Cirrhosis occurs more often in individuals with nonalcoholic steatohepatitis (NASH) than in those with steatosis (nonalcoholic fatty liver [NAFL]). The difference between NAFL and NASH is the extent of hepatocyte apoptosis, which is more extensive in NASH. Because phagocytosis of apoptotic cells activates hepatic stellate cells (HSCs), we examined the hypothesis that a pan-caspase inhibitor, VX-166, would reduce progression of fibrosis in a mouse model of NASH. Male db/db mice were fed methionine/choline-deficient (MCD) diets to induce NASH and liver fibrosis. Mice were gavaged once daily with either the pan-caspase inhibitor VX-166 (6 mg/kg/d; Vertex, Abingdon, UK) or vehicle only and sacrificed at 4 or 8 weeks. Treatment with an MCD diet increased alanine aminotransferase (ALT), caspase-3 activity, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, NASH, and fibrosis. Treatment of MCD-fed mice with VX-166 decreased active caspase-3, TUNEL-positive cells, and triglyceride content (P < 0.05). However, ALT levels were similar in VX-166-treated mice and vehicle-treated controls. Histological findings also confirmed that both groups had comparable liver injury (NAFLD activity score >or=6). Nevertheless, VX-166-treated MCD-fed mice demonstrated decreased alpha-smooth muscle actin expression (4 weeks, P < 0.05; 8 weeks, P < 0.005) and had reduced hepatic levels of collagen 1alpha1 messenger RNA (8 weeks, P < 0.05). Hydroxyproline content and Sirius red staining of VX-166-treated livers confirmed decreases in fibrosis. CONCLUSION: Inhibiting hepatic apoptosis suppresses the development of fibrosis in mice with NASH. Beneficial effects on liver fibrosis were associated with reductions in hepatic steatosis, but occurred without obvious improvement in liver injury. These findings are consistent with evidence that apoptosis triggers HSC activation and liver fibrosis and suggest that caspase inhibitors may be useful as an antifibrotic NASH therapy.

Effects of small increases in copper levels on culturable basidiomycetous yeasts in low-nutrient soils.

AIMS: Investigating the effect of perturbations, with relatively low Cu concentrations, on yeast community composition in low-nutrient virgin soil. METHODS AND RESULTS: Culturable soil yeast populations were monitored at an experimental site treated with the fungicide copper oxychloride (10 mg Cu per kg soil). Yeast numbers were unaffected by additional Cu; however, a shift in yeast community composition from Hymenomycetes to Urediniomycetes species occurred. Subsequent growth experiments conducted with a synthetic liquid medium revealed that hymenomycetous and urediniomycetous yeasts were affected differently by 1 and 10 mg l(-1) Cu. Soil microcosm experiments then indicated that additional 10 mg kg(-1) Cu may improve the competitive ability of urediniomycetous yeasts in the presence of hymenomycetous yeasts. CONCLUSIONS: The shift from hymenomycetous to urediniomycetous yeasts, as a result of slightly increased soil Cu levels, may be because of hymenomycetous yeasts being more sensitive to elevated Cu levels and urediniomycetous yeasts having an improved competitive ability in the presence of elevated Cu levels. SIGNIFICANCE AND IMPACT OF THE STUDY: Yeast community composition of pristine low-nutrient soils may change as a result of perturbations with relatively low concentrations of Cu. Urediniomycetous yeasts should be studied as potential bio-indicators of Cu perturbations.

Effects of different sleep restriction protocols on sleep architecture and daytime vigilance in healthy men.

Sleep is regulated by complex biological systems and environmental influences, neither of which is fully clarified. This study demonstrates differential effects of partial sleep deprivation (SD) on sleep architecture and psychomotor vigilance task (PVT) performance using two different protocols (sequentially) that each restricted daily sleep to 3 hours in healthy adult men. The protocols differed only in the period of sleep restriction; in one, sleep was restricted to a 3-hour block from 12:00 AM to 3:00 AM, and in the other, sleep was restricted to a block from 3:00 AM to 6:00 AM. Subjects in the earlier sleep restriction period showed a significantly lower percentage of rapid-eye-movement (REM) sleep after 4 days (17.0 vs. 25.7 %) and a longer latency to the onset of REM sleep (L-REM) after 1 day (78.8 vs. 45.5 min) than they did in the later sleep restriction period. Reaction times on PVT performance were also better (i.e. shorter) in the earlier SR period on day 4 (249.8 vs. 272 ms). These data support the view that earlier-night sleep may be more beneficial for daytime vigilance than later-night sleep. The study also showed that cumulative declines in daytime vigilance resulted from loss of total sleep time, rather than from specific stages, and underscored the reversibility of SR effects with greater amounts of sleep.

Pathologic findings and liver elements in hibernating bats with white-nose syndrome.

Two groups of vespertilionid bats were collected from affected hibernacula. In group 1 (n, 14; pathology and microbiology), the average body weights of all species were at the lower limit of published ranges. Twelve bats (86%) had mycotic growth in the epidermis, hair follicles, and sebaceous glands. Geomyces destructans, with its characteristic curved conidia, was observed microscopically, cultured, and confirmed by polymerase chain reaction. Dermatitis and mural folliculitis was nil to mild. When focally coinfected with Gram-negative bacteria, there was necrosis and pustules. Fat stores were little to abundant in 12 bats (86%) and nil in 2. Thirteen bats (93%) had pulmonary congestion and 7 (50%) had bone marrow granulocytosis. In group 2 (n, 24; liver elements), 3 bats (13%) had potentially toxic lead levels and 1 (4%), potentially toxic arsenic level. There was no evidence of major organ failure or consistent element toxicity.

Serologically defined (SD) locus in cattle.

Using cytotoxic serums obtained from multiparous cows or by alloimmunization, we have detected 11 lymphocyte antigens controlled by codominant alleles at a serologically defined locus called BoLA-A (bovine lymphocyte antigens). This locus, along with the lymphocyte defined loci previously reported, establishes the existence of a major histocompatibility system of cattle.

Lymphocyte-defined loci in cattle.

Using the results of all paired one-way mixed lymphocyte culture tests on families of half-sibs, we have established that the lymphocyte-defined system in cattle contains a minimum of two loci. The methodology presented is applicable to studies of the lymphocyte-defined systems of other species.

Beta-adrenergic receptor kinase: primary structure delineates a multigene family.

The beta-adrenergic receptor kinase (beta-ARK), which specifically phosphorylates only the agonist-occupied form of the beta-adrenergic and closely related receptors, appears to be important in mediating rapid agonist-specific (homologous) desensitization. The structure of this enzyme was elucidated by isolating clones from a bovine brain complementary DNA library through the use of oligonucleotide probes derived from partial amino acid sequence. The beta-ARK cDNA codes for a protein of 689 amino acids (79.7 kilodaltons) with a protein kinase catalytic domain that bears greatest sequence similarity to protein kinase C and the cyclic adenosine monophosphate (cyclic AMP)--dependent protein kinase. When this clone was inserted into a mammalian expression vector and transfected into COS-7 cells, a protein that specifically phosphorylated the agonist-occupied form of the beta 2-adrenergic receptor and phosphorylated, much more weakly, the light-bleached form of rhodopsin was expressed. RNA blot analysis revealed a messenger RNA of four kilobases with highest amounts in brain and spleen. Genomic DNA blot analysis also suggests that beta-ARK may be the first sequenced member of a multigene family of receptor kinases.

Anxiety levels in dreams: relation to changes in plasma free fatty acids.

Blood samples for determination of plasma free fatty acids were obtained throughout the night by means of an indwelling catheter. The first sample was drawn at the onset of rapid eye movements and a second after 15 minutes of these movements. Subjects were then awakened and asked to relate their dreams; a third sample was drawn 15 to 25 minutes later. Anxiety scores derived from 20 dreams of nine subjects had significant positive correlations with changes in free fatty acids occurring during REM sleep. No statistically significant relation was found between anxiety and the changes in free fatty acids occurring from the time just before awakening to 15 to 25 minutes later. Presumably, anxiety in dreams triggers the release of catecholamines into the circulation, and these catecholamines mobilize proportional amounts of free fatty acids from body fat.

Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.

In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (Phoenicopterus chilensis), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein-specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.

Ambrosiella beaveri, sp. nov., associated with an exotic ambrosia beetle, Xylosandrus mutilatus (Coleoptera: Curculionidae, Scolytinae), in Mississippi, USA.

Xylosandrus mutilatus is an Asian ambrosia beetle that has recently established in Mississippi, Texas, Alabama, and possibly Florida, USA. We investigated the fungi associated with the mycangia (specialized fungus-transporting structures) of X. mutilatus in Mississippi. Mycangia consistently yielded an Ambrosiella sp. which was subsequently found to be closely related to, but distinct from, other Ambrosiella species affiliated with Ceratocystis. This Ambrosiella is described herein as Ambrosiella beaveri sp. nov. Also isolated were Geosmithia lavendula, G. obscura, and a yeast, Candida homelintoma. It is likely Ambrosiella beaveri was introduced along with the beetle into North America.

Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.

Global and comparative protein profiles of the pronotum of the southern pine beetle, Dendroctonus frontalis.

The southern pine beetle (Dendroctonus frontalis Zimmermann) kills all pines within its range and is among the most important forest pest species in the US. Using a specialized mycangium surrounded by gland cells in the pronotum, adult females culture, transport, and inoculate two fungi into beetle galleries during oviposition. These fungal symbionts, to varying degrees, exclude antagonistic fungi and provide nutrients to larvae. However, the mechanisms (e.g. secreted antibiotic chemicals or nutrients, proteins or pathways) by which this relationship is maintained are not known. Here we present the first global and differential proteome profile of the southern pine beetle pronotum. Two-dimensional polyacrylamide electrophoresis, tandem mass spectrometry, and database searches revealed that the majority of pronotal proteins were related to energy-yielding metabolism, contractile apparati, cell structure, and defence. The identified proteins provide important insights into the molecular and biochemical processes of, and candidates for functional genomics to understand mycangia and pronotum functions in, the southern pine beetle.