Evaluation of Dynamic Arm Supports in Real Life Environments.

Dynamic arm supports facilitate the performance of activities of daily living (ADL) in people with upper extremity limitations. For which ADL, and how devices are used in daily life differs between users, imposing a difficulty to the assessment of outcomes. Therefore this study reports on the instruments used in earlier studies. Several instruments in the domains of body functions and activities and participation were identified. Instruments used include patient reported outcome measures, questionnaires, interviews, and arm and hand function tests.

Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function.

The isthmic organizer (IsO) is a signaling center that specifies the correct and distinct embryonic development of the dopaminergic midbrain and serotonergic hindbrain. The IsO is a linear boundary between the two brain regions, emerging at around embryonic day 7-8 of murine embryonic development, that shapes its surroundings through the expression of instructive signals such as Wnt and growth factors. Homeobox transcription factor engrailed 1 (En1) is present in midbrain and rostral hindbrain (i.e. rhombomere 1, R1). Its expression spans the IsO, and it is known to be an important survival factor for both dopaminergic and serotonergic neurons. Erroneous composition of dopaminergic neurons in the midbrain or serotonergic neurons in the hindbrain is associated with severe pathologies such as Parkinson's disease, depression or autism. Here we investigated the role of En1 in early mid-hindbrain development, using multiple En1-ablated mouse models as well as lineage-tracing techniques, and observed the appearance of ectopic dopaminergic neurons, indistinguishable from midbrain dopaminergic neurons based on molecular profile and intrinsic electrophysiological properties. We propose that this change is the direct result of a caudal relocation of the IsO as represented by ectopic presence of Fgf8, Otx2, Wnt1 and canonical Wnt-signalling. Our work suggests a newly-discovered role for En1: the repression of Otx2, Wnt1 and canonical Wnt-signaling in R1. Overall, our results suggest that En1 is essential for proper IsO maintenance and function.

The reliability and validity of the PALOC-s: a post-acute level of consciousness scale for assessment of young patients with prolonged disturbed consciousness after brain injury.

The objective of the study was the validation of the Post-Acute Level of Consciousness scale (PALOC-s) for use in assessing levels of consciousness of severe brain injured patients in a vegetative state or in a minimally conscious state. A cohort of 44 successively admitted patients (between 2 and 25 years of age), who were treated in an early intensive neurorehabilitation programme, were included in the study. Each patient was examined, using the Western Neuro Sensory Stimulation Profile (WNSSP) and the Disability Rating Scale (DRS), once every two weeks resulting in 327 examinations (all videotaped). To determine the reliability of the PALOC-s, six observers rated one videotape of each patient. One of the observers rated the same tapes a second time, 3-4 months later. Validity was determined by correlating 100 ratings of one observer with the scores on the WNSSP and the DRS. To determine the responsiveness of the PALOC-s, the size of change between the scores of the first and last examinations was calculated. The inter-observer correlations and agreement scores varied between .82 and .95. The intra-observer correlation and agreement scores varied between .94 and .96. Correlations with the WNSSP varied between .88 and .93, and with the DRS between .75 and .88. The responsiveness was significantly high (t=8.2), with a standardised effect size of 1.30. It is concluded that the PALOC-s is a reliable, valid, and responsive observation instrument provided it is administered after a structured assessment by an experienced and trained clinician. The PALOC-s is feasible for use in clinical management, as well as in outcome research.

Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a phosphatidylinositol 3-kinase (PI3) kinase-dependent manner in Neuro2a cells.

Insulin signalling is well studied in peripheral tissue, but not in neuronal tissue. To gain more insight into neuronal insulin signalling we examined protein kinase B (PKB) and extracellular regulated kinase 1 and 2 (ERK1/2) regulation in serum-deprived Neuro2a cells. Insulin phosphorylated PKB in a dose-dependent manner but reduced phosphorylation of ERK1/2. Both processes were phosphatidylinositol 3-kinase (PI3K) dependent. Interestingly, blockade of PI3K in combination with insulin induced phosphorylation of ERK1/2. The phosphorylation of ERK1/2 could be blocked with a specific inhibitor of mitogen-activated protein/ERK kinase (MEK), suggesting that it was mediated through the highly conserved Ras-Raf-MEK-ERK1/2 pathway. Prolonged exposure to high concentrations of insulin resulted in a desensitized PI3K-PKB route. The insulin-induced inhibition of ERK1/2 phosphorylation was also diminished when the PI3K-PKB route was desensitized. Blockade of PI3K in combination with insulin, however, still resulted in an unaltered MEK-dependent phosphorylation of ERK1/2. We conclude that PI3K is an important integrator of insulin signalling in Neuro2a cells as it regulates activation of PKB and inhibition of ERK1/2, and is sensitive to the duration of the insulin stimulus.

Impaired cutinase secretion in Saccharomyces cerevisiae induces irregular endoplasmic reticulum (ER) membrane proliferation, oxidative stress, and ER-associated degradation.

Impaired secretion of the hydrophobic CY028 cutinase invokes an unfolded protein response (UPR) in Saccharomyces cerevisiae cells. Here we show that the UPR in CY028-expressing S. cerevisiae cells is manifested as an aberrant morphology of the endoplasmic reticulum (ER) and as extensive membrane proliferation compared to the ER morphology and membrane proliferation of wild-type CY000-producing S. cerevisiae cells. In addition, we observed oxidative stress, which resulted in a 21-fold increase in carbonylated proteins in the CY028-producing S. cerevisiae cells. Moreover, CY028-producing S. cerevisiae cells use proteasomal degradation to reduce the amount of accumulated CY028 cutinase, thereby attenuating the stress invoked by CY028 cutinase expression. This proteasomal degradation occurs within minutes and is characteristic of ER-associated degradation (ERAD). Our results clearly show that impaired secretion of the heterologous, hydrophobic CY028 cutinase in S. cerevisiae cells leads to protein aggregation in the ER, aberrant ER morphology and proliferation, and oxidative stress, as well as a UPR and ERAD.

Pain-related correlates of MMPI profile subgroups among back pain patients.

The MMPI profiles of 96 male and 218 female patients attending a back pain clinic in a private university-affiliated, orthopedic hospital were analyzed by a hierarchical clustering procedure. The clustering procedure produced four male and four female profile subgroups. The subgroups were compared with one another on the basis of patients' responses to the Cornell Medical Index and revised McGill Pain Assessment Questionnaire. Within the male and female patient cohorts it was found that profile subgroups featuring elevated clinical scales showed greater disruptions of daily activities than did subgroups with relatively unelevated profiles. However, profile subgroups with elevations primarily on the neurotic triad scales reported greater affective disturbance and disruption of daily activities than did subgroups with elevations on both the neurotic triad and relatively psychotic scales. In addition, profile subgroups with subclinical elevations on the neurotic triad scales appeared to have adjusted to their pain experience more poorly than did subgroups that featured scores on nearly all clinical scales that were within one standard deviation of the mean. Suggestions are provided for the use of the MMPI in assessing chronic pain patients and future research regarding cluster analyses of patients' MMPI profiles.

Development of an attenuated apathogenic reovirus vaccine against viral arthritis/tenosynovitis.

A fully attenuated apathogenic reovirus vaccine was developed by 235 serial passages of S1133 strain avian reovirus in embryonating chicken eggs and 100 additional passages in chicken embryo fibroblast (CEF) cultures, 65 of which were cultured at 32 C. Chickens with and without maternal antibodies to avian reovirus were vaccinated subcutaneously at 1 day of age and challenged via footpad at 14 days of age. It appeared that the 40th, 66th, and 100th CEF passage levels were apathogenic at doses ranging from 10(2.5) to 10(6.8) TCID50/chick. No gross or microscopic lesions of tenosynovitis developed in vaccinated chicks. Vaccinated chicks were protected against challenge; unvaccinated control chickens were not.

Pulmonary congestion and edema (marble spleen disease) of chickens produced by group II avian adenovirus.

"Marble spleen disease" of chickens was diagnosed in 22-week-old chickens. Total mortality was 8.9%. Deaths occurred over a period of 2 months. Gross lesions included pulmonary congestion, splenomegaly, hepatomegaly, and congestion of egg follicles. Microscopic lesions included pulmonary congestion and edema, and reticuloendothelial cell hyperplasia of the spleen with concurrent white-pulp necrosis and lymphocyte depletion. The pulmonary lesions were of sufficient intensity to have caused the death of fatally affected birds. Many of the hyperplastic reticuloendothelial cells contained basophilic intranuclear inclusions similar to those that characterize hemorrhagic enteritis of turkeys, marble spleen disease of pheasants, and adenovirus group II splenomegaly of chickens. These characteristic lesions, plus serologic identification of the causal virus, indicate that "marble spleen disease" caused by avian group II adenovirus was affecting the flock under study. This appears to be the first report of death of chickens due to pulmonary congestion and edema caused by spontaneous infection with avian group II adenovirus.

Isolation of avian reovirus as a possible etiologic agent of osteoporosis ("brittle bone disease"; "femoral head necrosis") in broiler chickens.

Avian reovirus was isolated from intestines of 3-to-7-day-old broiler chickens with enteritis from broiler houses where osteoporosis was a problem. The virus was purified in a cesium chloride gradient (buoyant density 1.37 gm/ml) and identified as a reovirus by electron microscopy. Specific-pathogen-free (SPF) chickens and commercial broiler chickens with anti-reovirus maternal antibodies inoculated at 1 day of age with the reovirus isolate developed lesions of femoral head fractures and/or osteoporosis; reovirus could be reisolated from the bone marrow and intestinal tracts of experimentally infected SPF birds. The reovirus isolate, although isolated from intestines, induced development fo tenosynovitis lesions in SPF and commercial broiler chickens.

Pathogenicity for chickens of a reovirus isolated from turkeys.

A viral agent that was isolated from livers of commercial turkey poults that died at approximately two weeks of age was characterized as a reovirus. Experimental infection of day-old chickens with this reovirus isolate resulted in the development of tenosynovitis, hepatitis, and myocarditis. In vitro neutralization of the turkey reovirus isolate by antiserum against chicken reovirus correlated with in vivo protection of maternally immune chickens from day-old oral challenge with the turkey reovirus isolate.

Onset of progeny immunity against viral arthritis/tenosynovitis after experimental vaccination of parent breeder chickens and cross-immunity against six reovirus isolates.

Immunization of breeder chickens by eyedrop with viral arthritis/tenosynovitis vaccine strain S1133 (73rd egg passage) gave no immunity against day-old oral challenge of their progeny at 1 week postvaccination of the breeders, but progeny immunity was observed at 3, 4, 5, 6, and 7 weeks postvaccination of the breeders. Oral cross-challenge of immune progeny with viral isolates from Connecticut, West Virginia, California, Indiana, Pennsylvania, and Minnesota showed that in vitro neutralization of an isolate by anti-S1133 antiserum correlated with in vivo immunity of the progeny against oral day-old challenge with such an isolate.

Testicular changes of acute vitamin A deficiency of cockerels.

Sixty, 1-day-old Arbor Acres broiler cockerels, randomly allotted to three groups, were fed a vitamin A-deficient diet, vitamin A complete diet (control diet), or control diet pair-fed in an amount equal to the quantity consumed by the vitamin A-deficient group. Secondary sex characteristics, as indicated by comb enlargement, developed more rapidly in cockerels consuming the deficient diet. A difference in direct testicular weight was not observed between vitamin A-deficient birds and pair-fed controls, but the testicular weight relative to body weight and the level of testicular maturity were greater in the former. Ultrastructurally, lipid droplets were found in Sertoli cells and germinal epithelium of the deficient birds, but not the pair-fed controls. Paradoxically, serum testosterone concentrations were significantly reduced in sequential serum samples from vitamin A-deficient chicks, but not controls. The evidence indicated that vitamin A deficiency has an androgenic effect in cockerels despite reduced testosterone concentrations.

Field experiments with viral arthritis/tenosynovitis vaccination of breeder chickens.

Vaccination of three commercial broiler-breeder flocks at 15 weeks old with viral arthritis/tenosynovitis via the drinking water resulted in serologic conversion of two flocks to agar-gel-precipitin (AGP)-positive, while the third flock was still AGP-negative at 24 weeks, but was AGP-positive at 30 weeks old, presumably as a result of natural exposure. Progeny from the two successfully vaccinated breeder flocks remained free of clinical viral arthritis/tenosynovitis and had average condemnation rates of 0.99%. In contrast, six hatches of progeny from the third breeder flock experienced clinical viral arthritis/tenosynovitis and average condemnation rates of 3.64%.

Adaptation of enzyme-linked immunosorbent assay to the avian system.

A microplate enzyme-linked immunosorbent assay was developed to detect chicken anti-rovirus antibodies. Studies of the parameters which affect the outcome of the assay with avian serum revealed two aspects for a successful assay. First, enzyme-antibody conjugates prepared by the periodate oxidation technique were found to have retained far more immunological activity than conjugates produced by a glutaraldehyde cross-linking. Second, the results indicated an unusually high affinity of chicken immunoglobulin for the microplate plastic which was mostly eliminated by a pretreatment technique with fixed fetal calf serum. The enzyme-linked immunosorbent assay compared favorably with the latex passive agglutination test, yielding a titration endpoint of 1:511,000, or approximately 1,300 times more sensitive than the latex passive agglutination assay. The assay proved not only to be sensitive to less than 1 ng of specific antibody, but also to have low to moderate variance and high reliability.

An enzyme-linked immunosorbent assay (ELISA) for detecting chicken anti-reovirus antibody at high sensitivity.

An enzyme-linked immunosorbent assay (ELISA) with high sensitivity was developed for use in the avian system. Anti-reovirus antibody produced in chickens against the isolants S1133, UMI-203, Reo-25, and Winterfield were detected with this method at high titers (up to 1:14,000).

Viral arthritis/tenosynovitis: a review.

A review if presented of viral arthritis/tenosynovitis, one of the clinical manifestations of avian reovirus infection in chickens. Since the detection of a viral etiology of arthritis/tenosynovitis in 1957, the disease has been reported in various parts of the world. Pathological features of the disease include inflammatory lesions in the extensor and flexor tendons and tendon sheaths of the posterior limbs and in the tibiotarsal joints. Hepatitis, myocarditis, hydropericardium, as well as intestinal and respiratory tract involvement are described in association with avian reovirus infection. The epizootiology, horizontal and vertical transmission of reovirus, as well as the role of maternal immunity and its application in breeder vaccination for the control of viral arthritis/tenosynovitis are described.

Infectious tenosynovitis (viral arthritis): influence of maternal antibodies on the development of tenosynovitis lesions after experimental infection by day-old chickens with tenosynovitis virus.

When chicks with maternal antibodies against infectious tenosynovitis (viral arthritis) virus were inoculated orally at 1 day old with tenosynovitis virus, they were protected against developing active tenosynovitis lesions 3 weeks later. They were not protected against subcutaneous inoculation, however. Breeder vaccination against tenosynovitis resulted in immunity of the progeny against oral infection at 1 day old, whereas progeny from unvaccinated breeders were susceptible to such a challenge.

Infectious tenosynovitis in commercial White Leghorn chickens.

Infectious tenosynovitis was diagnosed in three separate outbreaks in a commercial White Leghorn hens, though not previously reported in adult White Leghorns (3). Clinically affected flocks had decreased production and increased daily mortality, with many hens showing signs of the so called "cage-fatigue bluecomb" syndrome. Most sick birds had lesions typical of infectious tenosynovitis, with pronounced cyanosis and dehydration. Dead birds had signs of acute septicemia. The course of the disease (about 8 weeks) was not altered by the medicinal regimens tried. Young laying-age flocks were most seriously affected. Production losses averaged 15 to 20%, and mortality reached 5% per month during the recovery phase.