Mutation analysis of feline Niemann-Pick C1 disease

Niemann-Pick C (NPC) disease is an autosomal recessive neurovisceral lysosomal storage disorder that results in defective intracellular transport of cholesterol. The major form of human NPC (NPC1) has been mapped to chromosome 18, the NPC1 gene (NPC1) has been sequenced and several mutations have been identified in NPC1 patients. A feline model of NPC has been characterized and is phenotypically, morphologically, and biochemically similar to human NPC1. Complementation studies using cultured fibroblasts from NPC affected cats and NPC1 affected humans support that the gene responsible for the NPC phenotype in this colony of cats is orthologous to human NPC1. Using human-based PCR primers, initial fragments of the feline NPC cDNA were amplified and sequenced. From these sequences, feline-specific PCR primers were generated and designed to amplify six overlapping bands that span the entire feline NPC1 open reading frame. A single base substitution (2864G-C) was identified in NPC1 affected cats. Obligate carriers are heterozygous at the same allele and a PCR-based assay was developed to identify the geneotype of all cats in the colony. The mutation results in an amino acid change from cysteine to serine (C955S). Several of the mutations identified in people occur in the same region. Marked similarity exists between the human and feline NPC1 cDNA sequences, and is greater than that between the human and murine NPC1 sequences. The human cDNA sequence predicts a 1278aa protein with a lysosomal targeting sequence, several trans-membrane domains and extensive homology with other known mediators of cholesterol homeostasis.     

Prognostic significance of del(20q) in patients with hematological malignancies

Deletions of the long arm of chromosome 20 represent a common chromosomal abnormality associated with myeloid malignancies, in particular with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Using G-banding cytogenetic techniques, we found clones with del(20q) in 36 patients with hematological malignancies examined in our laboratory during the years 2001–2003: in 23 patients as a sole cytogenetic aberration and in 13 patients together with other chromosomal changes. Fluorescence in situ hybridization (FISH) with a probe specific for the 20q12 region was used in all cases to confirm the presence of the clone with deletion. For patients with additional or complex chromosomal rearrangements, multicolor FISH (M-FISH) analysis was performed. Statistical evaluation of the prognostic impact of sex, age, diagnosis, and karyotype was performed. The survival time correlated with the type of chromosomal aberration; no significant differences in survival were found for sex, age, and diagnosis.     

Coordinated Strategy for a Model-Based Decision Support Tool for Coronavirus Disease,Utah, USA

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state’s response to ongoing outbreaks and can be applied in other settings to address unique public health challenges.     

Measuring distortion of skeletal elements in Lodox Statscan‐generated images

Due to a scarcity of available skeletal material, anthropologists and other practitioners face difficulties with either the creation or validation of techniques used to estimate a biological profile in subadults. To address this problem, radiographic images of living individuals are often used in lieu of dry skeletal elements. However, radiographic images suffer from distortion. Some problems with metric analyses when using radiographic images may be addressed with the Lodox Statscan, an X‐ray machine that claims to produce minimal distortion along the scan‐axis due to a linear slot‐scanning design. The purpose of this research was to measure the distortion of skeletal elements in radiographic images generated from a Lodox Statscan. Skeletal elements subject to multiple imaging variables that affect distortion were radiographed, measured, and then compared to the dry bone measurements through multiple approaches. An 85% percent agreement within a ±1 mm range and a 97% agreement within a ±2 mm range was obtained. Percent difference results demonstrate that slot‐axis measurements incurred more distortion than scan‐axis measurements (11.8% and 2.7%, respectively). Inclusion of foam results in 4.5% more error than when foam is not included in the image. Angled scan‐axis measurements also incurred more distortion than either nonangled slot‐ and scan‐axis measurements. A Bland‐Altmanplot reveals an overall agreement between the radiographic and dry bonemeasurements, with most measurements falling within the upper and lower limits. Similar measurement error is found in Statscan radiographic and dry bone measurements; therefore, the Statscan offers a radiographic venue to collect metric data. Clin. Anat. 26:780–786, 2013. © 2013 Wiley Periodicals, Inc.     

The Feasibility and Validity of Body-Worn Sensors to Supplement Timed Walking Tests for Children with Neurological Conditions

Aims: The 10-meter walk test (10 mWT) and Timed Up and Go (TUG) are assessments of speed/time with a ceiling effect in pediatric populations. This study aimed to (1) determine whether collecting spatiotemporal data with inertial sensors (Mobility Lab, APDM Inc.) during these tests improves their discriminative validity, and (2) evaluate the clinical feasibility of Mobility Lab. Methods: Fifteen children with spina bifida (SB) or cerebral palsy (CP) (7.9 ± 3.1 years old) and fifteen age- and sex-matched typically-developing (TD) children completed the 10 mWT and TUG wearing Mobility Lab. Spatiotemporal data were compared between groups. Mobility Lab's potential to distinguish children with SB/CP from TD children was examined using conditional logistic regression. Feasibility was evaluated through participant adherence and a clinical utility scale. Results: For the 10 mWT, group differences (p < 0.01) were found in horizontal and frontal trunk range of motion, horizontal trunk velocity, and swing asymmetry. Children with SB/CP took significantly longer to turn during the TUG. These five variables together distinguished the two groups (p = 0.006). 78% of participants with SB/CP completed the testing protocol. Mobility Lab scored 4/10 on the clinical utility scale. Conclusions: Instrumenting the 10 mWT and TUG improves the tests’ ability to discriminate between children with SB/CP and TD children.     

Examining Young Recreational Sportswomen's Intentions to Engage in Sun-Protective Behavior: The Role of Group and Image Norms

Researchers examined the sun-protective intentions and behavior of young, Caucasian, Australian sportswomen aged between 17 and 35 years (N?=?100). The study adopted a 2 x 2 experimental design, comparing group norms (supportive vs. non-supportive) and image norms (tanned vs. pale) related to sun protection and taking into account group identification with friends and peers in the sport. While no significant findings emerged involving image norms, regression analyses revealed a significant two-way interaction for group norm x identification on recreational sportswomen's intentions to engage in sun protection in the next fortnight. Participants identifying strongly with their group had stronger intentions to engage in sun protection when exposed to a norm reflecting fellow recreational sportswomen engaging in sun-protective actions in comparison to those exposed to a non-supportive group. In addition, while prior intentions to engage in sun protection were not significantly related to sun-protection behavior, post-manipulation intentions after exposure to the sun-protective information that was provided were significantly related to follow-up behavior. Overall, the findings supported the importance of group-based social influences, rather than tanned media images, on sun-protective decisions among young recreational sportswomen and provided a targeted source for intervention strategies encouraging sun safety among this at-risk group for repeated sun exposure.     

A theory-based intervention to promote medication adherence in patients with rheumatoid arthritis: A randomized controlled trial

Clinical Rheumatology - Adherence to prescribed medication regimens is fundamental to the improvement and maintenance of the health of patients with rheumatoid arthritis. It is therefore important...