A scoping review to explore how universal design for learning is described and implemented by rehabilitation health professionals in school settings.

BACKGROUND: Universal design for learning (UDL) is a framework that provides guidelines to support children with diverse needs in the classroom and promotes inclusion of all children. Although UDL is recognized as a promising approach for school-based rehabilitation health professionals (RHPs), there are no studies that synthesize evidence on the use of UDL by RHPs in the school setting. Therefore, the research question for this study is: How is UDL described and implemented in school settings by RHPs? This study specifically examined literature from occupational therapy, physiotherapy, and speech-language pathology. METHODS: A scoping review was completed to (a) summarize how UDL is described in the rehabilitation literature, (b) summarize the recommended and reported role of RHPs in the delivery of UDL, and (c) identify gaps in the evidence base. CINAHL, Embase, MEDLINE, PsychINFO, Sociological Abstracts, Web of Science, and ERIC electronic databases were searched. Numerical summaries and theoretical thematic analysis were used to describe the data both quantitatively and qualitatively. RESULTS: Inclusion criteria were achieved for 45 of the 3,998 screened documents. Most of the included documents lacked a definition of UDL. Analysis suggested that speech-language pathologists and occupational therapists implement UDL in a variety of ways within the school setting. No physiotherapy literature was found, and limited high-level empirical research has been conducted within rehabilitation. CONCLUSION: This scoping review provides a broad understanding of how RHPs describe and implement UDL-aligned services in school settings. UDL is a promising framework that provides RHPs with guidance on how to support children with diverse needs in the classroom, with the overall aim to promote inclusion of all children. There is a need for further research to determine the effectiveness of UDL as implemented by RHPs and to examine the role of physiotherapists in using UDL-type services.

Applications of the first digit law to measure correlations.

The quasiempirical Benford law predicts that the distribution of the first significant digit of random numbers obtained from mixed probability distributions is surprisingly meaningful and reveals some universal behavior. We generalize this finding to examine the joint first-digit probability of a pair of two random numbers and show that undetectable correlations by means of the usual covariance-based measure can be identified in the statistics of the corresponding first digits. We illustrate this new measure by analyzing the correlations and anticorrelations of the positions of two interacting particles in their quantum mechanical ground state. This suggests that by using this measure, the presence or absence of correlations can be determined even if only the first digit of noisy experimental data can be measured accurately.

Long-term monitoring of captive red drum Sciaenops ocellatus reveals that calling incidence and structure correlate with egg deposition.

In the present study, quantitative data were collected to clarify the relationship between calling, call structure and eggs produced in a captive population of red drum Sciaenops ocellatus. Sciaenops ocellatus were held in four tanks equipped with long-term acoustic loggers to record underwater sound throughout a simulated reproductive season. Maximal sound production of captive S. ocellatus occurred when the photoperiod shifted from 13·0 to 12·5 h of light, and the water temperature decreased to c. 25° C. These captive settings are similar to the amount of daylight and water temperatures observed during the autumn, which is the primary spawning period for S. ocellatus. Sciaenops ocellatus exhibited daily patterns of calling with peak sound production occurring in the evenings between 0·50 h before dark and 1·08 h after dark. Spawning occurred only on evenings in which S. ocellatus were calling, and spawning was more productive when S. ocellatus produced more calls with longer durations and more pulses. This study provides ample evidence that sound production equates to spawning in captive S. ocellatus when calls are longer than 0·8 s and contain more than seven pulses. The fact that more calling, longer calls and higher sound pressure levels are associated with spawns that are more productive indicates that acoustic metrics can provide quantitative information on spawning in the wild.

Influence of selection for breast muscle mass on myosin isoform composition and metabolism of deep pectoralis muscles of male and female turkeys.

Advances in genetic selection and nutrition have resulted in rapid growth rates and increased muscle mass, predisposing turkeys to muscle disorders such as deep pectoral myopathies and increasing the incidence of pale, soft, and exudative muscle. The objective of this study was to determine if selection for breast muscle mass created an increase in anaerobic capacity of the deep pectoralis muscle. A total of 67, 18-wk-old, male and female turkeys from two male (tom) lines and one female (hen) line were used. Each bird was anesthetized and one deep pectoralis muscle was electrically stimulated via the pectoral nerve. Muscle pH was recorded every 30 s for 4 min of stimulation and every 1 min for a 10-min recovery period. Non-stimulated muscles, contralateral to the stimulated side, were assayed for lactate dehydrogenase (LDH) and glyceraldehyde phosphate dehydrogenase (GAPDH). Myosin isoforms were resolved with SDS-PAGE. Line or gender had no effect on rate of pH decline during or after stimulation. Declines in pH during stimulation were greater than during the recovery period (0.06 vs. 0.02 U/min). The lightweight male line (LM) had the greatest breast muscle mass as a percentage of body weight (P < 0.05) and the greatest LDH [293 mmol nicotinamide adenine dinucleotide (NADH) min(-1)microg(-1); P < 0.0001] and GAPDH (0.4452 mmol NADH min(-1)microg(-1); P < 0.05) activities. Hens had greater percentages breast weight than males (P < 0.05) and a tendency for increased enzyme activities. The LM line had the largest ratio (2.33:1) (P < 0.05) of adult-to-neonatal myosin. Genetic selection for breast muscle mass resulted in an increased ratio of adult-to-neonatal myosin and increased anaerobic capacity. This effect on myosin isoform composition and anaerobic capacity supports handling modifications that are line specific to minimize meat quality defects.

Subjective overachievement: individual differences in self-doubt and concern with performance.

We discuss the construct of doubt about one's competence and suggest that doubt can have myriad consequences (e.g., self-handicapping, defensive pessimism). We focus on the effect of self-doubt when it is combined with a concern with performance and assert that this combination leads to the phenomenon of subjective overachievement. In two studies, we present a new 17-item Subjective Overachievement Scale (SOS), which includes two independent subscales measuring individual differences in self-doubt and concern with performance. The first study, consisting of two large samples (Ns = 2,311 and 1,703), provides evidence that the scale has high internal consistency and a clear two-factor structure. Additionally, the subscales have adequate test-retest reliability (Ns = 67 and 115). A second study reveals that the SOS has good convergent and discriminant validity. Both subscales are unrelated to social desirability but exhibit the predicted patterns of associations with other related constructs. The Concern with Performance Subscale is correlated with achievement motivation, whereas the Self-Doubt Subscale is correlated with scales assessing negative affectivity (e.g., self-esteem, social anxiety) and other self-related strategies associated with concerns about one's competence (e.g., self-handicapping, defensive pessimism, impostor phenomenon). The SOS, which combines the two subscales, appears to tap a unique strategy that individuals may use to deal with doubts about their own competence.

Advances in the diagnosis and management of scleroderma-related vascular complications.

Vascular disease is observed in virtually all patients with systemic sclerosis and presents several challenges for the clinician. The alterations in vascular tone noted with Raynaud's phenomenon may have corollaries in both the pathogenesis and management of systemic sclerosis-related internal organ complications. Early recognition of isolated pulmonary hypertension, coronary microcirculatory disease, and scleroderma renal involvement may be the keys to successful outcomes. Future trends in the management of systemic sclerosis may be directed at preventing the development of these vascular syndromes. This may occur through combined therapies directed at the abnormal immune response, disregulated fibroblast function, and resultant abnormal vascular response.

Structure-function studies of interleukin 15 using site-specific mutagenesis, polyethylene glycol conjugation, and homology modeling.

Interleukin (IL)-15 is a multifunctional cytokine that shares many biological activities with IL-2. This functional overlap, as well as receptor binding subunits shared by IL-15 and IL-2, suggests tertiary structural similarities between these two cytokines. In this study, recombinant human IL-15 was PEGylated via lysine-specific conjugation chemistry in order to extend the circulation half-life of this cytokine. Although PEGylation did extend the beta-elimination circulation half-life of IL-15 by greater than 50-fold, the biological activity of polyethylene glycol (PEG)-IL-15 was significantly altered. Specifically, PEG-IL-15 lost its ability to stimulate the proliferation of CTLL but took on the properties of a specific IL-15 antagonist in vitro. In comparing sequence alignments and molecular models for IL-2 and IL-15, it was noted that lysine residues resided in regions of IL-15 that may have selectively disrupted receptor subunit binding. We hypothesized that PEGylation of IL-15 interferes with beta but not alpha receptor subunit binding, resulting in the IL-15 antagonist activity observed in vitro. The validity of this hypothesis was tested by engineering site-specific mutants of human IL-15 as suggested by the IL-15 model (IL-15D8S and IL-15Q108S block beta and gamma receptor subunit binding, respectively). As with PEG-IL-15, these mutants were unable to stimulate CTLL proliferation but were able to specifically inhibit the proliferation of CTLL in response to unmodified IL-15. These results supported our model of IL-15 and confirmed that interference of beta receptor subunit binding by adjacent PEGylation could be responsible for the altered biological activity observed for PEG-IL-15.

Visualization and comparison of molecular dynamics simulations of leukotriene C4, leukotriene D4, and leukotriene E4.

Molecular dynamics simulations of leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4) were carried out, and the data were visualized in an animated video format. Three-dimensional ghost images show the positions of the heavy atoms of all three molecules throughout the simulations. The ghost images can be superimposed to give a single three-dimensional image in which the shapes of the most populated conformers of each molecule are apparent and can be compared. Leukotriene D4 was found to occupy mostly T-shaped conformations, while LTC4 occupied mostly cup-shaped conformations, and LTE4 occupied a wide range of conformations spanning the LTD4 and LTC4 types. Digital filtering and graphing of the internal geometries of the molecules as a function of time revealed differences in dynamic behavior. The results are discussed in light of current knowledge about leukotriene receptors.

Inhibition of endothelial cell proliferation by SPARC is mediated through a Ca(2+)-binding EF-hand sequence.

SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin and BM-40) is a metal-binding glycoprotein secreted by a variety of cultured cells and characteristic of tissues undergoing morphogenesis, remodeling, and repair. Recently it has been shown that SPARC inhibits the progression of the endothelial cell cycle in mid-G1, and that a synthetic peptide (amino acids 54-73 of secreted murine SPARC, peptide 2.1) from a cationic, disulfide-bonded region was in part responsible for the growth-suppressing activity [Funk and Sage (1991): Proc Natl Acad Sci USA 88:2648-2652]. Moreover, SPARC was shown to interact directly with bovine aortic endothelial (BAE) cells through a C-terminal EF-hand sequence comprising a high-affinity Ca(2+)-binding site of SPARC and represented by a synthetic peptide (amino acids 254-273) termed 4.2 [Yost and Sage (1993): J Biol Chem 268:25790-25796]. In this study we show that peptide 4.2 is a more potent inhibitor of DNA synthesis that acts cooperatively with peptide 2.1 to diminish the incorporation of [3H]-thymidine by both BAE and bovine capillary endothelial (BCE) cells. At concentrations of 0.019-0.26 mM peptide 4.2, thymidine incorporation by BAE cells was decreased incrementally, relative to control values, from approximately 100 to 10%. Although somewhat less responsive, BCE cells exhibited a dose-responsive decrement in thymidine incorporation, with a maximal inhibition of 55% at 0.39 mM. The inhibitory effect of peptide 4.2 was essentially independent of heparin and basic fibroblast growth factor and was blocked by anti-SPARC peptide 4.2 IgG, but not by antibodies specific for other domains of SPARC. To identify residues that were necessary for inhibition of DNA synthesis, we introduced single amino acid substitutions into synthetic peptide 4.2 and tested their activities and cell-surface binding characteristics on endothelial cells. Two peptides displayed null to diminished effects in the bioassays that were concentration-dependent: peptide 4.2 K, containing an Asp258 --> Lys substitution, and peptide 4.2 AA, in which the two disulfide-bonded Cys (positions 255 and 271) were changed to Ala residues. Peptide 4.2 K, which failed to fulfill the EF-hand consensus formula, exhibited an anomalous fluorescence emission spectrum, in comparison with the wild-type 4.2 sequence, that was indicative of a compromised affinity for Ca2(+).(ABSTRACT TRUNCATED AT 400 WORDS)

Purification of biologically active SPARC expressed in Saccharomyces cerevisiae.

SPARC (secreted protein, acidic and rich in cysteine) is a secreted, Ca+2-binding glycoprotein that modulates interactions between cells and their immediate extracellular matrix. Traditional sources of SPARC have been mammalian bone, platelets, a basement membrane tumor, and cultured cells; most if not all preparations, however, contain platelet-derived growth factor and one or more serum proteins that bind specifically to purified SPARC. To avoid these contaminants, as well as the toxic lipid moiety associated with endotoxin, we expressed recombinant wild-type and a mutated murine SPARC in two strains of Saccharomyces cerevisiae: one strain was transfected with an expression vector encoding a proprietory signal peptide that directed the secretion of the recombinant protein. Recombinant SPARC was also purified from cell lysates of a different, nonreverting strain of S. cerevisiae that was optimized for large-scale fermentation runs. A mutant murine SPARC lacking the single glycosylation site was also expressed following substitution of Asn98 with Asp98 in the wild-type sequence. Purification of SPARC was achieved by copper-affinity and hydrophobic-interaction chromatography. Both the wild-type and the glycosylation-defective recombinant proteins exhibited high levels of activity in two bioassays with endothelial cells: inhibition of cell spreading/disruption of actin microfilaments and competition for the binding of nonrecombinant 125I-labeled SPARC to the cell surface. The availability of biologically active, recombinant SPARC will facilitate investigation of the structural and functional properties of this protein, which is expressed at high levels in healing wounds, atherosclerotic plaque, and several cancers and diseases of connective tissue.

Specific interaction of SPARC with endothelial cells is mediated through a carboxyl-terminal sequence containing a calcium-binding EF hand.

SPARC is a secreted, Ca(2+)-binding protein that modulates cell shape and gene expression (Sage, E.H., and Bornstein, P. (1991) J. Biol. Chem. 266, 14831-14834). In the present study we questioned whether SPARC interacted with an endothelial cell surface receptor. The binding of 125I-SPARC to bovine aortic endothelial cells was dependent on Ca2+ and was sensitive to small changes in extracellular pH; maximal binding occurred at pH 7.1. Scatchard analysis indicated approximately 2.3 x 10(7) binding sites/cell with an apparent KI of 1.1 nM. The interaction was diminished specifically by competition with synthetic peptides corresponding to amino acids 54-73 (SPARC 54-73) and 254-273 (SPARC254-273). The binding of 125I-SPARC254-273, a sequence containing a Ca(2+)-binding EF-hand, was saturated within 45 min at a concentration of 5 microM; Scatchard analysis indicated 4.2 x 10(7) sites/cell and a KI of 2.4 nM. Iodinated proteins from plasma membranes were affinity-chromatographed on SPARC254-273; several proteins with apparent masses ranging from 153 to 100 kDa (unreduced) or from 153 to 122 kDa (reduced) were eluted with the soluble peptide. These proteins represent candidates for a SPARC receptor(s) that mediates the biological activity of this protein on endothelial cells.

Vascular steal mimicking compression myelopathy in Paget's disease of bone: rapid reversal with calcitonin and systemic steroids.

Neurologic manifestations of Paget's disease of bone are primarily a result of mechanical compression on cranial nerves, spinal cord and roots. Less recognized is a myelopathy from "vascular steal" to highly vascularized and hypermetabolic pagetic bone. We describe a case of presumed ischemic myelitis in a patient with Paget's disease and aortic stenosis that was rapidly reversed with subcutaneous calcitonin and intravenous dexamethasone.

Diagnosis and management of vascular disease in systemic sclerosis.

Vascular disease is seen in virtually all patients with systemic sclerosis and presents several challenges to physicians caring for them. Early recognition of isolated pulmonary hypertension and scleroderma renal crisis may be keys to successful outcomes. Although complete reversal of vascular disease is usually not possible, the availability of calcium channel blocking agents for RP and isolated pulmonary hypertension and ACE inhibitors for hypertensive renal disease has improved the morbidity and mortality of these patients. Optimal management of the vascular events in systemic sclerosis will ultimately depend on a clearer understanding of their pathogenesis. Treatment may ultimately be directed at preventing the development of these vascular syndromes. This may occur through combined therapy directed at both the abnormal immune response and disregulated fibroblast function seen in the disease, as well at the abnormal vascular responses. Such therapies have yet to be identified.

Substratum-induced stress fiber assembly in vascular endothelial cells during spreading in vitro.

We tested whether aortic endothelial cell (EC)-synthesized substrata, which modulate smooth muscle cell proliferation and EC motility following injury, could influence EC actin cytoskeleton and spreading in vitro. A partial characterization of the substrata indicates that the substratum prepared by deoxycholic acid extraction (DOC-derived substratum) is enriched with fibronectin and type IV collagen. Substratum prepared by removal of the intact monolayer with 20 mM EGTA in PBS (EGTA-derived substratum) contains fibronectin and heparan sulfate proteoglycan, but no type IV collagen. Morphometric analyses were performed on fixed and cytoskeletal antibody treated EC in order to quantitate the extent of spreading and stress fiber (SF) assembly. Compared to plastic, the DOC-derived substratum, a collagenase-treated DOC-derived substratum (CT-DOC-derived substratum) and the EGTA-derived substratum promote EC spreading 2.3-, 2.9- and 1.7-fold, respectively. In addition, there are 4.2-, 4.1- and 2.0-fold more SF on DOC-, CT-DOC- and EGTA-derived substrata, respectively, when compared to plastic. Subcellular fractionation and immunoprecipitation of cytoskeletal proteins from metabolically labeled EC were performed prior to electrophoresis and fluorography. The DOC-derived substratum increases immunoprecipitable actin and myosin 3- to 4.5-fold in both fractions compared to the EGTA-derived substratum and plastic. Collagenase treatment of the DOC-derived substratum partially inhibits this increase. Cycloheximide treatment prevents the rise in soluble actin and myosin as well as causing a reduction in SF number by 1/2 on the DOC-derived substratum and 2/3 on CT-DOC-derived substratum. We propose that fibronectin-collagen interactions are, in part, responsible for inducing endothelial synthesis of cytoskeletal proteins required for SF assembly. This substratum-induced actin-cytoskeletal reorganization facilitates EC spreading in vitro.

Age-related and site-specific adaptation of the arterial endothelial cytoskeleton during atherogenesis.

The authors probed the vascular endothelial cell cytoskeleton in strains of pigeons that are atherosclerosis-susceptible and disease-resistant, namely, the White Carneau and Show Racer pigeons. Endothelial cell actin and myosin were localized with the use of affinity-purified antibodies in conjunction with indirect immunofluorescence microscopy. The endothelial cell cytoskeleton was characterized in a site-specific and time-dependent manner by examination of arterial segments from each strain of pigeons. Anti-actin and anti-myosin fluorescence staining patterns of endothelial cells lining the ascending aorta, aortic arch, and thoracic aorta from the White Carneau and Show Racer pigeons sacrificed at 1 and 12 months of age were compared and analyzed. In the Show Racer, irrespective of arterial site or chronologic age, endothelial cell cytoskeletal organization is similar. Actin and myosin fluorescence is brightest at the cortex, where endothelial cells meet their neighbors. There is also an amorphous (diffuse) fluorescence throughout the cytoplasm. In addition to the diffuse and cortical cytoskeletal fluorescence in the endothelial cells of the Show Racers, the White Carneau also possess a unique cytoskeletal array of linear fluorescence, ie, the endothelial cell ridge. At 1 month of age, anti-actin staining of endothelial cell ridges averages 28.5 mu in length in the ascending aorta, 28.0 mu in the aortic arch, and 40.0 mu in the thoracic aorta. At the same time, anti-myosin fluorescence extends past both ends of the anti-actin-stained endothelial cell ridge fluorescence. In the ascending aorta, anti-myosin labeling of endothelial cell ridges is 3.5 times longer than anti-actin staining. This staining is absent in the aortic arch, whereas the thoracic aorta possesses endothelial cell ridges that extend over the entire length of the vessel segment. At 12 months of age, actin-stained endothelial cell ridges increase 1.6- and 1.4-fold in the ascending aorta and aortic arch, respectively. The thoracic aorta possesses endothelial cell ridges that cover its entire length. At 12 months of age, the length of myosin-stained endothelial cell ridges does not increase in the ascending or thoracic aorta. In contrast, the aortic arch expresses endothelial cell ridges that exceed 150 mu in length. It is proposed that the endothelial cell ridge assembles from cytoskeletal components as a focal endothelial cell response to injury, perhaps promoting endothelial cell adhesion to the underlying basal lamina through a transmembrane linkage.

Saturable and nonsaturable copper and calcium transport in mouse duodenum.

Duodenal copper and calcium absorption was evaluated in 30-day-old normal male Swiss mice by an in situ loop procedure. For both ions, the 90-min absorption values yielded a curve that was resolvable into a hyperbolic (saturable) and a linear (nonsaturable) function. The two ions differed, however, in total absorption and the relative importance of the two functions. For copper, the maximum saturable component of transepithelial movement (Jmax) was 127 +/- 2.4 (SE) pmol in 90 min, the apparent half-saturation constant of the saturable process (Kt) was 4.3 +/- 0.7 microM, and the slope of the nonsaturable function was 0.011 +/- 0.006. Thus, when luminal copper equaled plasma copper (approximately equal to 15 microM), only 8% was absorbed, nearly all of which was by the saturable component. For calcium, on the other hand, Jmax was 4.8 +/- 0.1 mumol, the Kt was 27 +/- 2 mM, and the slope was 0.10 +/- 0.01. At luminal calcium concentrations equal to the inorganic plasma calcium (1 mM), calcium absorption was 75%, but only 80% of that was moved by the saturable process. The findings suggest the existence of separate transport mechanisms for copper and calcium.