Resilience in Families with Children and Adult Members with Intellectual Disabilities: Tracing Elements of A Psycho‐Social Model

Aim This paper seeks to illumine how families with children and adult members with intellectual disabilities manage to manifest a buoyant and durable capacity over time. It is therefore concerned centrally with the idea of resilience. Method Drawing from diverse theoretical literatures from child development and protection and gerontology, the paper begins with a review of constructions of resilience. In an attempt to assess where there seems to be support for resilience in families, the core of the paper tests empirical evidence about positive experiences of families supporting children and adults with intellectual disabilities against the theoretical literature on resilience. Result and Conclusions The findings are used to suggest conditions under which resilience is produced and maintained, and to identify emergent elements of a psycho‐social model of resilience in families with children and adult members with intellectual disabilities.     

Characterization of autoantibodies against sulfatide from a V-gene phage-display library derived from patients with systemic lupus erythematosus

Sulfatide, ceramide galactosyl-3'-sulfate, is mainly present in nervous tissue, kidney, testis, red blood cells, platelets and granulocyte. Antibodies to sulfatide are present in many patients with demyelinating peripheral neuropathy, HIV infection and systemic lupus erythematosus and may account for some of the clinical manifestations. To evaluate the effect of such antibodies, we have constructed a phage-display antibody fragment library from the lymphocytes of patients with systemic lupus erythematosus. Sulfatide-reactive phage were selected by absorption and elution on sulfatide liposomes and soluble single chain variable fragment (ScFv) were isolated from individual colonies and tested in an ELISA assay for binding to bovine brain sulfatide. Five ScFv clones that bound sulfatide were isolated. Two of the clones, PH5 and PA38, bound sulfatide but not phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin or ceramide. These two clones also bound sulfatide from human red blood cells. The DNA encoding the fragments was sequenced, revealing predicted polypeptides of 19 kDa for PH5 containing only variable heavy (VH) sequences, and 31 kDa for PA38, with both VH and variable light (VL) sequences. Although they had similar antigen specificities, the VH domains of the two clones were derived from different heavy-chain families. The clustered mutational patterns in the complementarity-determining region (CDR) of the heavy chains in both clones suggest that the V-domains are the products of antigen-driven B cell clonal maturation leading to the development of sulfatide-binding specificity. These results show the presence of sulfatide-specific antibodies in lupus patients, and allow us to test the possibility that the interaction of the antibodies with sulfatide may contribute to some of the symptoms. In addition, the antibodies provide useful reagents to test the role of sulfatide in pathophysiological processes.     

The pharmacology of RS-15385-197, a potent and selective α2-adrenoceptor antagonist

1 RS-15385-197 ((8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(methylsul- phonyl)-6H-isoquino [2,1-g][1,6]-naphthyridine) was evaluated in a series of in vitro and in vivo tests as an antagonist at α₂-adrenoceptors.2 RS-15385-197 had a pK_i of 9.45 for α₂-adrenoceptors in the rat cortex (pA₂ in the guinea-pig ileum of 9.72), whereas the 8aS, 12aR, 13aR enantiomer, RS-15385-198, had a pK_i of only 6.32 (pA₂ 6.47) indicating a high degree of stereoselectivity. The racemate RS-15385-196 had a pK_i of 9.18.3 RS-15385-197 showed unprecedented α₂ vs. α₁ adrenoceptor selectivity in vitro. In the rat cortex, RS-15385-197 had a pK_i of 9.45 in displacing [³H]-yohimbine and 5.29 in displacing [³H]-prazosin (α₂/α₁ selectivity ratio in binding experiments > 14000). The compound had a pA₂ of 9.72 as a competitive antagonist of the inhibitory effects of UK-14,304 in transmurally-stimulated guinea-pig ileum and 10.0 against BHT-920-induced contractions in dog saphenous vein (DSV); this latter value was unaltered by phenoxybenzamine. An apparent pK_B of 5.9 was obtained against cirazoline-induced contractions in DSV, whilst a pA₂ of 6.05 was obtained against phenylephrine-induced contractions in the rabbit aorta (α₂/α₁ selectivity ratio in functional experiments > 4000).4 RS-15385-197 was highly selective for α₂-adrenoceptors over other receptors: the compound showed low affinity for 5-HT_1A (pK_i 6.50) and 5-HT_1D (pK_i 7.00) receptor subtypes, and even lower affinity (pK_i≤5) for other 5-HT receptor subtypes, dopamine receptors, muscarinic cholinoceptors, β-adrenoceptors and dihydropyridine binding sites. RS-15385-197 was devoid of affinity for the non-adrenoceptor imidazoline binding site, labelled by [³H]-idazoxan, which provides further evidence that these sites are not related to α₂-adrenoceptors. In the DSV, contractile responses to 5-hydroxytryptamine (5-HT) were unaffected by a concentration of 1 μM RS-15385-197.5 RS-15385-197 was non-selective for the α_2A- and α_2B-adrenoceptor subtypes in that the pK_i for the α_2A-adrenoceptor in human platelets was 9.90 and the pK_i for the α_2B-adrenoceptor in rat neonate lung was 9.70. However, RS-15385-197 showed lower affinity for the α₂-adrenoceptor subtype in hamster adipocytes (pK_i 8.38).6 In anaesthetized rats, RS-15385-197 was a potent antagonist of the mydriasis response induced by UK-14,304 or clonidine (AD₅₀ 5 and 7 μg kg^-1, i.v., respectively; 96 μg kg^-1, p.o.) and of UK-14,304-induced pressor responses in pithed rats (AD₅₀ 7 μg kg^-1, i.v.); the compound therefore is both centrally and orally active. Even at a high dose (10 mg kg^-1, i.v.), RS-15385-197 did not antagonize pressor responses to cirazoline in pithed rats, indicating that the selectivity for α₂ vs. α₁-adrenoceptors was maintained in vivo.8 RS-15385-197 is therefore a very potent, selective, competitive α₂-adrenoceptor antagonist, both in vitro and in vivo, is orally active and readily penetrates the brain. It will thus be a powerful pharmacological tool for exploring the various physiological roles of α₂-adrenoceptors.     

Rheumatoid factor (antigammaglobulin) in women. Effects of oral contraceptive use on its prevalence

A total of 14,856 women, including 921 pregnant subjects, were tested for rheumatoid factor; 4,562 were using oral contraceptives at the time of testing. The prevalence of rheumatoid factor increased directly with age. The age-adjusted prevalence of rheumatoid factor was lower in oral contraceptive users than in nonusers but this difference was not statistically significant. Rheumatoid factor remained positive in 39% of subjects undergoing retesting after an average interval of 16 months. Those women with higher titers of rheumatoid factor were more likely to remain positive (81%). Of the women having positive tests, 5.4% were identified as having rheumatoid disease.     

Health-related quality of life in children with cerebral palsy and their families

Objective

To determine the health-related quality of life in children with cerebral palsy and their families.

Methods

One hundred children (3–10 years of age) receiving regular rehabilitation therapy for cerebral palsy for last 1 year at a Child Development Centrer were enrolled and the Lifestyle assessment questionnaire — cerebral palsy was administered to the parents.

Results

9% had good, 24% had mildly-affected, 37% had moderately-affected and 30% had severely-affected healthrelated quality of life. The physical independence, mobility and social integration dimensions were much more severely affected than the clinical burden, economic burden and schooling dimensions.

Conclusion

Health-related quality of child is affected in most children with cerebral palsy.     

Diagnostic accuracy of somatosensory evoked potential and electroencephalography during carotid endarterectomy

Background and Purpose: Perioperative stroke risk following carotid endarterectomy (CEA) is reported to be approximately 2–3%. The diagnostic accuracies of intraoperative EEG and SSEP monitoring during CEA have been studied separately. However, to date, the effectiveness of simultaneous EEG and SSEP monitoring during CEA has only been evaluated in small study populations. This study examined the diagnostic accuracy of combined EEG and SSEP monitoring in a large (N = 1165) patient population.

Methods: This study included 1165 patients who underwent CEA from 2000 to 2012 at the University of Pittsburgh Medical Center. The sensitivities, specificities, and diagnostic odds ratio of EEG and SSEP monitoring methods were examined separately and together. Receiver operating characteristic curves were plotted to assess sensitivity and specificity of single and combined Intraoperative monitoring (IONM) methods.

Results: Maximum sensitivity was obtained with multimodality monitoring with an IONM change in either EEG or SSEP of 50.00 (95% CI, 30.66–69.34). The specificity of simultaneous EEG and SSEP changes was 93.95 (95% CI, 92.28–95.35%). Maximum area under ROC curve obtained for IONM change in either EEG or SSEP was 0.660 (95% CI, 0.547–0.773, p-value 0.004).

Conclusion: The diagnostic accuracy of multimodality IONM during CEA is higher than an approach using single modality IONM. Simultaneous EEG and SSEP monitoring improves the likelihood of detecting periprocedural strokes after CEA. Neuro protective therapies to prevent periprocedural strokes can be based on changes in SSEP and EEG during CEA.     

Experimental and finite element analysis of dynamic loading of the mouse forearm

Bone formation is reported to initiate in osteocytes by mechanotransduction due to dynamic loading of bone. The first step towards this is to characterize the dynamic strain fields in the overall bone. Here, the previously developed mouse forearm ulna‐radius model, subjected to static loading, has been further enhanced by incorporating a loading cap and applying a cyclic dynamic load to more closely approximate experimental biological conditions. This study also incorporates data obtained from strain gauging both the ulna and radius simultaneously. Based on separate experiments, the elastic modulus of the ulna and radius were determined to be 13.8 and 9.9 GPa, respectively. Another novel aspect of the numerical model is the inclusion of the interosseous membrane in the FE model with membrane stiffness ranging from 5–15 N/mm that have been found to give strain values closer to that from the experiments. Interestingly, the inclusion of the interosseous membrane helped to equalize the peak strain magnitudes in the ulna and radius (～1800 at 2 N load and ～3200 at 3.5 N), which was also observed experimentally. This model represents a significant advance towards being able to simulate through FE analysis the strain fields generated in vivo upon mechanical loading of the mouse forearm. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1580–1588, 2014.     

Adhesion of platelets to surface-bound fibrinogen under flow

After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.