Understanding the impact of an intergenerational arts and health project: a study into the psychological well-being of participants, carers and artists.

OBJECTIVES: There is growing interest in arts practices in relation to public health, including their potential to support psychological well-being. This study sought to understand the impact of Hear and Now, an intergenerational arts and health project, upon indicators of psychological well-being among all groups involved: young people, older people with a diagnosis of dementia and their carers and partners and the project's artistic team. STUDY DESIGN: This was a descriptive exploratory qualitative study, using focus groups and observation as data collection methods. METHODS: Study participants were 65 people representing the four groups participating in the 2019 Hear and Now project: older adults living with a diagnosis of dementia, their carers and partners, young people and a team of professional artists and facilitators. Of these, 27 participated in one or more of seven focus groups. Participants were asked about their previous engagement with music and dance, thoughts about the intergenerational element of the project and other aspects of their experiences that related to indicators of well-being. In order to investigate the project's impact on participants' well-being, Seligman's PERMA model was adopted, which sets out five indicators of well-being: positive emotions, engagement, positive relationships, meaning and achievement/accomplishment. RESULTS: Experiences relating to all five areas of the PERMA model were evidenced by all groups in relation to their involvement in the project. Additional health benefits were also cited by some, as well as enhanced perceptions of other members of the project cohort. CONCLUSIONS: The findings support existing literature that intergenerational and arts activities can be beneficial for individuals' psychological health. Experiences relating to all five dimensions of the PERMA model of well-being (positive emotion, engagement, positive relationships, meaning, achievement/accomplishment) were cited by the four participant groups, which suggests examining the impact of such projects on all project collaborators is worthy of further study. Understanding the impact these projects can have on the various groups involved will enable artistic and healthcare communities to better collaborate and value each other's practices.

Wildlife disease. Recent introduction of a chytrid fungus endangers Western Palearctic salamanders.

Emerging infectious diseases are reducing biodiversity on a global scale. Recently, the emergence of the chytrid fungus Batrachochytrium salamandrivorans resulted in rapid declines in populations of European fire salamanders. Here, we screened more than 5000 amphibians from across four continents and combined experimental assessment of pathogenicity with phylogenetic methods to estimate the threat that this infection poses to amphibian diversity. Results show that B. salamandrivorans is restricted to, but highly pathogenic for, salamanders and newts (Urodela). The pathogen likely originated and remained in coexistence with a clade of salamander hosts for millions of years in Asia. As a result of globalization and lack of biosecurity, it has recently been introduced into naïve European amphibian populations, where it is currently causing biodiversity loss.

Dendritic spine alterations in neocortical pyramidal neurons following postnatal neuronal Nogo-A knockdown.

The myelin-associated protein Nogo-A is a well-known inhibitor of axonal regeneration and compensatory plasticity, yet functions of neuronal Nogo-A are not as clear. The present study examined the effects of decreased levels of neuronal Nogo-A on dendritic spines of developing neocortical neurons. Decreased Nogo-A levels in these neurons resulted in lowered spine density and an increase in filopodial type protrusions. These results suggest a role for neuronal Nogo-A in maintaining a spine phenotype in neocortical pyramidal cells.

MRI of childhood dacryocystocele.

We report an unusual presentation of a dacryocystocele in a 3-day-old child, with clinical and novel MRI findings. The literature contains extensive CT documentation, but descriptions of the MRI appearances of dacryocystoceles are lacking. Although CT is the standard initial imaging modality, MRI can be helpful if there are questions as to the content of the lesion or a need for further anatomical characterization.

Phobic anxiety in 11 nations. Part I: Dimensional constancy of the five-factor model.

The Fear Survey Schedule-III (FSS-III) was administered to a total of 5491 students in Australia, East Germany, Great Britain, Greece, Guatemala, Hungary, Italy, Japan, Spain, Sweden, and Venezuela, and submitted to the multiple group method of confirmatory analysis (MGM) in order to determine the cross-national dimensional constancy of the five-factor model of self-assessed fears originally established in Dutch, British, and Canadian samples. The model comprises fears of bodily injury-illness-death, agoraphobic fears, social fears, fears of sexual and aggressive scenes, and harmless animals fears. Close correspondence between the factors was demonstrated across national samples. In each country, the corresponding scales were internally consistent, were intercorrelated at magnitudes comparable to those yielded in the original samples, and yielded (in 93% of the total number of 55 comparisons) sex differences in line with the usual finding (higher scores for females). In each country, the relatively largest sex differences were obtained on harmless animals fears. The organization of self-assessed fears is sufficiently similar across nations to warrant the use of the same weight matrix (scoring key) for the FSS-III in the different countries and to make cross-national comparisons feasible. This opens the way to further studies that attempt to predict (on an a priori basis) cross-national variations in fear levels with dimensions of national cultures.

GT3 and its O-acetylated derivative are the principal A2B5-reactive gangliosides in cultured O2A lineage cells and are down-regulated along with O-acetyl GD3 during differentiation to oligodendrocytes.

Among the developmentally regulated antigens expressed on the surface of bipotential glial precursors isolated from neonatal rat brain are the gangliosides recognized by the monoclonal antibody A2B5. Immunostaining of thin layer chromatograms showed that oligodendrocyte-type 2 astrocyte (O2A) progenitors in culture express two ganglioside antigens that react strongly with the A2B5 antibody. Both ganglioside antigens are down-regulated as the cells differentiate to oligodendrocytes, corresponding to the disappearance of cell surface immunostaining by A2B5 in mature oligodendrocytes. By contrast, both gangliosides continue to be expressed when the cells differentiate to type-2 astrocytes. These two A2B5-reactive gangliosides in O2A lineage cells were identified as GT3 and O-acetyl GT3 by using the monoclonal antibody 18B8 that recognizes GT3 and an influenza C virus esterase that specifically removes O-acetyl moieties from sialic acids. Thin-layer chromatographic immunostaining with the JONES monoclonal antibody demonstrated that the progenitor cells in culture also express O-acetyl GD3, which is similarly down-regulated in oligodendrocytes, but retained in type-2 astrocytes. The 18B8 and JONES antibodies also immunostained the surface of O2A progenitors. Therefore, expression of GT3 and O-acetylation of GT3 and GD3 occur during the proliferative and migratory stages of glial cell development. Published 1999 Wiley-Liss, Inc.

Microdeletion of chromosome sub-band 2q37.3 in two patients with abnormal situs viscerum.

We report on two cases of microdeletion of chromosome sub-band 2q37.3 with abnormal situs viscerum. The first patient had dextrocardia, duodenal and jejunal atresia, and an abdominal hernia. The liver was in the left upper quadrant, stomach in the right upper quadrant. In contrast anema the ascending colon was in the left, and descending colon on the right, with an area of atresia in the mid-jejunum. The second patient had malrotation and malposition of large and small bowel, with most of the bowels positioned above the liver and spleen. There was incomplete rotation of the cecum. The right kidney was malrotated and mal-positioned. The finding of 2q37.3 deletion in both patients implies that a locus or loci involved in the development of normal body situs lies within this chromosome region. Molecular cytogenetic evaluation for a possible 2q37.3 deletion should be considered in patients with abnormal situs viscerum.

Single-molecule detection with a two-photon fluorescence microscope with fast-scanning capabilities and polarization sensitivity.

We describe a laser-scanning two-photon fluorescence microscope that is capable of observing single molecules with excellent temporal resolution and three-dimensional spatial resolution. To demonstrate the capabilities of the instrument we present single-molecule fluorescence data obtained in several different scanning modes. In addition, a polarization-sensitive detection scheme can provide detailed three-dimensional information about the orientations of molecules in any of these scanning modes.

Biochemical and morphometric analyses show that myelination in the insulin-like growth factor 1 null brain is proportionate to its neuronal composition.

To elucidate the role of insulin-like growth factor 1 (IGF1) in the normal development of brain myelination, we used behavioral, biochemical, and histological analyses to compare the myelination of brains from Igf1(-/-) and wild-type (WT) littermate mice. The studies were conducted at postnatal day 40, at which time the Igf1(-/-) mice weighed approximately 66% less than wild-type mice. However, the Igf1(-/-) brain weight was only reduced by approximately 34%. Formal neurological testing showed no sign of central or peripheral myelinopathy in Igf1(-/-) mice. Myelin composition was not significantly different, and myelin concentration, normalized to brain weight or protein, was equal in Igf1(-/-) and WT mice. Likewise, concentrations of myelin-specific proteins (MBP, myelin proteolipid protein, MAG, and 2',3'-cyclic nucleotide,3'-phosphodiesterase) were not significantly different in Igf1(-/-) and WT mice. The myelin-associated lipids galactocerebroside and sulfatide were modestly reduced in Igf1(-/-) brains. Regional oligodendrocyte populations and myelin staining patterns were comparable in Igf1(-/-) and WT brains, with the notable exception of the olfactory system. The Igf1(-/-) olfactory bulb was profoundly reduced in size and was depleted of mitral neurons and oligodendrocytes, and its efferent tracts were depleted of myelin. In summary, this study shows that myelination of the Igf1(-/-) brain is proportionate to its neuronal composition. Where projection neurons are preserved despite the deletion of IGF1, as in the cerebellar system, oligodendrocytes and myelination are indistinguishable from wild type. Where projection neurons are depleted, as in the olfactory bulb, oligodendrocytes are also depleted, and myelination is reduced in proportion to the reduced projection neuron mass. These data make a strong case for the primacy of axonal factors, not including IGF1, in determining oligodendrocyte survival and myelination.

Cross-pin femoral fixation: a new technique for hamstring anterior cruciate ligament reconstruction of the knee.

A new method of femoral fixation for arthroscopic anterior cruciate ligament (ACL) reconstruction using semitendinosus and gracilis (ST/G) tendons is presented. Biomechanical evaluation of the method was performed with pullout tests using animal tissues simulating fixation of ST/G tendons passing around a 2.5-mm pin placed transversely through a femoral tunnel. Clinical assessment of 22 patients was performed according to IKDC, Tegner, Lysholm, isokinetic strength, and KT1000 standards. Fixation strengths ranged from 725 N to 1,600 N for yield and maximal loads to failure for 35-mm to 70-mm cross-pins. Clinical results at mean follow-up of 30 months showed one traumatic failure, IKDC 86% normal or nearly normal, Tegner 6 ave, Lysholm 93 ave, KT1000 86% < 3 mm side-to-side difference on maximal manual evaluation, and isokinetic strength testing of quadriceps 8% deficit with hamstrings 8% deficit. Cross-pin fixation of ST/G tendons may be one of the strongest modes of femoral graft attachment yet devised. Our clinical outcomes in this initial series compare well with previous reports of ACL reconstruction regardless of graft or technique.

Expression of sulfated gangliosides in the central nervous system.

Several sulfated lipids were detected in the ganglioside fraction isolated from a cell line of oligodendrocyte progenitors that had been metabolically labeled with [35S] sulfate. Separation of the ganglioside fraction by two-dimensional TLC showed that, except for galactosylceramide-sulfate, none of the sulfate-labeled lipids comigrated with those glycosphingolipids visualized by orcinol staining, indicating that these sulfolipids were quantitatively minor components. At least eight sulfate-labeled lipid bands were susceptible to desialylation by Arthrobacter ureafaciens neuraminidase, which resulted in the formation of three new bands that retained the labeled sulfate. Six of the sulfate-labeled lipid bands containing sialic acid were also susceptible to Vibrio cholerae neuraminidase, which generated two labeled bands that appeared identical to the two major products formed after treatment with A. ureafaciens neuraminidase. In vivo labeling of lipids from 14-day-old rat brain with [35S]-sulfate demonstrated that the synthesis of sulfated lipids containing sialic acid also occurred in intact brain tissue. These results show that sulfated gangliosides are synthesized in the CNS and that oligodendrocytes are one cell type that contributes to this synthesis.

A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy.

Eleven patients with demyelinating polyneuropathy associated with monoclonal IgM antibodies were randomized to receive IVIg or placebo, monthly, for 3 months in a double-blind study. After a washout period, they crossed over to the alternate therapy. Response was gauged by evaluating muscle strength, sensation, and neuromuscular symptoms at baseline, after 3 months, and at treatment's end. After IVIg therapy, the strength improved in only 2 of 11 patients, by 28 and 38.5 points from baseline, and declined after placebo. In 1 other patient, the sensory score improved by 13 points. Antibody titers to MAG/SGPG or gangliosides did not appreciably change. We conclude that IVIg has only a modest benefit to not more than 18% of patients with IgM paraproteinemic demyelinating neuropathy.

Extracellular matrix upregulates synthesis of glucosylceramide-based glycosphingolipids in primary Schwann cells.

The formation of basement membrane around Schwann cells that are in contact with axons is necessary for Schwann cell differentiation and myelin formation in the peripheral nervous system. However, primary Schwann cells grown on basement membrane in the absence of neuronal influence show increased proliferation rather than differentiation, which implies that the signals generated by Schwann cell-basement membrane interactions are multipotential. We examined the effect of matrigel, an exogenous basement membrane preparation, and other extracellular matrix growth surfaces on primary Schwann cells to determine if the resulting interactions play a role in the control of glycosphingolipid synthesis. Isolated primary Schwann cells grown on a thin layer of matrigel rapidly adhered to the surface and exhibited a greater degree of cell spreading when compared to cells grown on the nonspecific substrate polylysine. Labeling of the cells with [3H]galactose between 24 and 48 hr after plating revealed that the incorporation of [3H]galactose into glucosylceramide-based glycosphingolipids increased from 1.5-3-fold on matrigel in comparison to cells grown on polylysine. The major labeled glycolipids under both conditions were GM3 ganglioside and two neutral glycolipids that comigrated with GbOse4Cer (GalNAc beta 1-3Gal alpha 1-4Gal beta 1-1Cer) and GbOse5Cer (GalNAc alpha 1-3Gal-NAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer) standards. There was little or no increase in the incorporation of [3H]leucine, [3H]galactose, or [3H]glucosamine into proteins or [3H]palmitic acid into phospholipids, free ceramides, or sphingomyelin, suggesting that the matrigel-induced increase in the synthesis of the glycolipids was selective. In the absence of serum, there was little or no difference in the levels of glycolipid labeling between cells grown on the two substrata, demonstrating that serum factors were required for matrigel to have this effect. When cells were grown on surfaces coated with individual extracellular matrix components, those cells grown on laminin and collagen IV showed an increase in glycolipid labeling similar to that produced by matrigel, while labeling increased to a lesser degree for the other components tested. Thus, the signals generated by interactions between Schwann cells and basement membrane, particularly the laminin and collagen IV constituents, contribute to the regulation of glycolipid synthesis which in turn may affect cell morphology and proliferation.

Multiple antibodies to nerve glycoconjugates in a patient with neuropathy and monoclonal IgA gammopathy.

Several immunological abnormalities were found in a patient with mixed axonal and demyelinating neuropathy in association with a prominent monoclonal IgA lamda band in his serum. He had antibodies to the major LM1 ganglioside of human nerve that were restricted to the IgA class, but they were polyclonal and distinct from the major monoclonal IgA component. He also had a low level of a monoclonal IgM lamda antibody to the myelin-associated glycoprotein and sulfate-3-glucuronyl paragloboside that was not detected by routine immunofixation. The observations made on this complex patient, are presented in the context of emphasizing that immunological reactivities to neural antigens that are not due to the principal monoclonal antibody may be present in patients with neuropathy in association with gammopathy.

Effects of brefeldin A on galactosphingolipid synthesis in an immortalized Schwann cell line: evidence for different intracellular locations of galactosylceramide sulfotransferase and ceramide galactosyltransferase activities.

Brefeldin A (BFA) has been used extensively to study the intracellular transport and processing of proteins and sphingolipids because of its dramatic alteration of the structural and functional organization of the Golgi. We have examined the effect of BFA on the synthesis of galactosylceramide sulfate (SGalCer) and its immediate precursor galactosylceramide (GalCer) in an immortalized Schwann cell line (S16) to determine the intracellular sites of synthesis of these two related glycolipids. During a 6-h labeling period, a dose-dependent inhibition of [35S]sulfate incorporation into SGalCer was observed with 95% inhibition occurring at 0.5 microgram/ml BFA. Labeling of newly synthesized galactosphingolipids with [3H]-palmitic acid for 6 h in the presence of BFA resulted in increased incorporation of label into GalCer containing nonhydroxy fatty acids (NFA-GalCer) to 162% of control values, whereas labeling of GalCer containing 2-hydroxy fatty acids (HFA-GalCer) was reduced to 63% of control. After 24 h, these values were at 366 and 91%, respectively. These results indicate that at least some of the HFA-GalCer was initially synthesized at a location distal to the BFA block and separate from the site of NFA-GalCer synthesis. Examination of [3H]palmitic acid incorporation into free ceramides showed an increase of 133 and 161% for hydroxy and nonhydroxy fatty acid ceramides, respectively, in cells treated for 6 h with BFA in comparison with levels found in untreated control cells, indicating that BFA did not block fatty acid 2-hydroxylation or the formation of HFA ceramide.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of glycolipids and myelin-associated glycoprotein during the differentiation of oligodendrocytes: comparison of the CG-4 glial cell line to primary cultures.

The expression of cerebrosides, sulfatides, gangliosides and the myelin-associated glycoprotein (MAG) during differentiation of the CG-4 line of oligodendrocyte progenitors [Louis et al.: J. Neurosci Res 31: 193, 1992] was compared with their expression in primary cultures of oligodendrocyte precursors [McCarthy and de Vellis: J Cell Biol 85: 890, 1980]. When the CG-4 cells differentiated from bipolar progenitors to oligodendrocytes, there was a decrease of glucosylcerebroside synthesis and an increase in galactosylcerebroside and sulfatide synthesis. However, even after differentiation, the incorporation of [3H]galactose into these glycolipids, the amounts of galactosylcerebroside and sulfatide, and the galactocerebroside/sulfatide ratio were all much less than in primary cultures of differentiating oligodendrocytes. The major gangliosides in differentiated primary oligodendrocyte cultures were GM3 and GD3, and GD3 was also a major ganglioside in the CG-4 line. However, unlike primary cultures of O-2A lineage cells in which GM3 synthesis increased dramatically during differentiation to oligodendrocytes, the CG-4 cells expressed very little GM3. Also, the CG-4 cells expressed larger amounts of more complex gangliosides, e.g. GD1b and GT1b, which were almost entirely restricted to the b-series. The amount of MAG expressed by the CG-4 cells increased substantially when they differentiated to oligodendrocytes, and it was almost all the large immature isoform. However, even after differentiation, the amount expressed was less than in differentiated primary oligodendrocyte cultures. Overall, the lower expression of myelin-related glycolipids and MAG by the CG-4 line suggests a lesser degree of differentiation in comparison to primary oligodendrocytes under the culture conditions of these experiments, but the larger amounts of cells available from the CG-4 line should be useful for investigating glycolipid and MAG function related to the early stages of myelinogenesis.

Differentiation of oligodendrocytes cultured from developing rat brain is enhanced by exogenous GM3 ganglioside.

Cultures consisting primarily of O-2A progenitor cells and immature oligodendrocytes with a few microglia and astrocytes were obtained by shaking primary cultures from neonatal rat brain after 12-14 days in vitro. Addition of 50 micrograms/ml exogenous Neu-NAc alpha 2-3Gal beta 1-4Glc beta 1-1'ceramide (GM3 ganglioside) to the cultures resulted in an increase in the number and thickness of cell processes that stained intensely for sulfatide and galactocerebroside (galC) in comparison to control cultures without added GM3. The treated cultures also contained fewer astrocytes than control cultures as revealed by immunostaining for glial fibrillary acidic protein (GFAP). Cells that immunostained for both GFAP and sulfatide/galC were very rare in control cultures but were frequently seen in the GM3-treated cultures, suggesting that these may represent cells changing their direction of differentiation away from type II astrocytes toward oligodendrocytes under the influence of GM3. These effects on the developing rat oligodendrocytes were specific for GM3 ganglioside and were not produced by adding GM1, GM2, GD3, or GD1a to the cultures. Lactosyl ceramide and neuraminyl lactose were also ineffective. When control cultures were initially plated on polylysine and incubated with [14C]galactose, GD3 was the principal labeled ganglioside. However, as the control cells differentiated over time in culture without the addition of exogenous GM3 and produced increasing amounts of myelin-related components, the incorporation of [14C]galactose into endogenous GM3 increased to become the predominant labeled ganglioside by 6 days after plating. Metabolic labeling of the GM3-treated oligodendrocytes with [14C]galactose revealed increased incorporation into galC and sulfatide in comparison to control cultures, but a decreased labeling of endogenous GM3. Similarly, incorporation of an amino acid precursor into the myelin-associated glycoprotein (MAG) was increased by GM3 treatment, but incorporation into myelin basic protein (MBP) was not affected. Although the overall effect of added GM3 was to decrease the phosphorylation of most proteins in the oligodendrocytes, including MBP, GM3 enhanced the phosphorylation of MAG. These findings indicate that GM3 ganglioside has an important role in the differentiation of cells of the O-2A lineage toward myelin production, since differentiation is associated with increased metabolic labeling of endogenous GM3 in control cultures and is enhanced by the addition of exogenous GM3.

Childhood ataxia with diffuse central nervous system hypomyelination.

A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.

Sensory neuropathy associated with monoclonal immunoglobulin M to GD1b ganglioside.

A 67-year-old woman with a sensory polyneuropathy was shown to have a serum monoclonal immunoglobulin M lambda antibody with a titer of 1:10,000 toward GD1b ganglioside. The immunoglobulin M also reacted with some other gangliosides containing disialosyl groups such as GD2, GD3, and GQ1b, but it did not react with GM1, LM1, or GD1a. The principal reactive ganglioside in human cauda equina was GD1b.

Entry of newly synthesized gangliosides into myelin.

Ganglioside synthesis and transport to myelin was studied in brainstem slices prepared from 19-21-day-old rats. The slices were incubated for up to 2 h in the presence of [3H]glucosamine to label primarily the hexosamine portion of complex gangliosides. The amount of radioactivity incorporated into gangliosides during slice incubations was only 10-15% of the amount of the label incorporated during in vivo labeling of brainstem gangliosides using equivalent amounts of [3H]glucosamine. Among individual gangliosides this inhibition was greater for the more complex gangliosides. When labeled gangliosides were isolated from homogenate and myelin fractions prepared from brain slices, the complex total gangliosides of both fractions showed a lag in labeling kinetics but with a lower specific radioactivity for the myelin fraction, reflecting the larger pool size and slower turnover rate exhibited by myelin components. Chase experiments showed that more complex gangliosides in homogenate exhibited almost no effect of chase after 30 min. Addition of the Golgi-disrupting agent monensin to slice incubations inhibited the labeling of all gangliosides except GM3, GM2, and GD3, and transport to myelin of all complex gangliosides except GM2. These results show that a monensin-sensitive mode of transport is responsible for the translocation of most newly synthesized gangliosides into myelin.