Enzymatic activity toward poly(L-lactic acid) implants

Tissue reactions toward biodegradable poly(L-lactic acid) implants were monitored by studying the activity pattern of seven enzymes as a function of time: alkaline phosphatase, acid phosphatase, -naphthyl acetyl esterase, -glucuronidase, ATP-ase, NADH-reductase, and lactate dehydrogenase. Cell types were identified by their specific enzyme patterns, their morphology and location. Special attention was paid to the enzyme patterns of macrophages, fibroblasts and polymorphonuclear granulocytes (PMNs), being involved in foreign body reactions or inflammatory responses. One day after implantation, an influx of neutrophilic and eosinophilic granulocytes was observed, coinciding with activity of alkaline phosphatase (PMN's) and -glucuronidase (eosinophils). From day 3 on, macrophages containing ATP-ase, acid phosphatase and esterase could be observed. From day 7 on, lactate dehydrogenase, the enzyme normally involved in the conversion of lactic acid, and its coenzyme NADH-reductase were observed in macrophages and fibroblasts. These two enzymes demonstrated more activity than expected on basis of wound-healing reactions upon implantation of a nonbiodegradable, inert biomaterial (as, e.g., Teflon). It is concluded that the biodegradable poly (L-lactic acid) used in these implantation studies is tissue compatible, and evokes a foreign body reaction with minor macrophage and giant cell activity, as observed during this 3-week implantation period. Most enzyme patterns were simply due to a wound-healing reaction. The slightly increased levels of LDH and NADH suggest the release of lactic acid from the implant, and thus confirms the biodegradable nature of this polymer

IMPORTANZA CLINICA DELLA TIPIZZAZIONE SIEROLOGICA E MOLECOLARE DELLE VARIANTI DELL'ANTIGENE RhD

Il sistema Rh, dopo quello ABO, è il sistema gruppo-ematico eritrocitario più immunogeno dell’uomo. Infatti all’esecuzione del gruppo ABO si accompagna sistematicamente la contemporanea determinazione del fenotipo Rh. L’antigene più importante del sistema Rh, l’antigene D, è molto più efficace di qualunque altro antigene eritrocitario nel determinare una risposta anticorpale quando venga introdotto in un soggetto che ne è privo. Esso è presente sugli eritrociti dell’85% delle persone di razza bianca ed in percentuale ancora più alta in quelle di razza nera . Quindi dopo gli antigeni A e B, il D è il più importante nella pratica trasfusionale. Diversamente dagli antigeni A e B, tuttavia, le persone che non possiedono l’antigene D sui propri eritrociti non presentano, regolarmente, l’anti-D. La formazione dell’anticorpo anti-D origina dall’esposizione, per motivi trasfusionali o gravidanze, ad emazie che presentano l’antigene D. E’ stato stimato che dal 30 all’85% delle persone D negative che ricevono una trasfusione D positiva svilupperà l’anti-D. Per questo motivo, tutti i riceventi e tutti i donatori di sangue vengono esaminati, nelle procedure di routine, per la presenza dell’antigene D, al fine di assicurare che i riceventi D negativi vengano identificati e ricevano sangue D negativo. L’antigene D è stato da sempre oggetto di studio dell’immunoematologia. L’interesse verso tale antigene è aumentato dopo la scoperta che alcuni individui RhD positivi producevano in seguito a trasfusioni anticorpi anti-D. Successivi studi portarono alla scoperta del mosaicismo dell’antigene RhD e rivelarono la sua grande variabilità (D partial e D weak). In passato, i limiti delle metodiche sierologiche non consentirono di identificare le molte varianti dell’antigene D, che perciò venivano identificate come D negativo. Questo non rappresentava un problema nell’individuo ricevente la trasfusione, dato che veniva trasfuso con sangue RhD negativo (come riceventi alcune varianti sono tutt’ora trattate come RhD negative), ma creava un problema se l’individuo era un donatore di sangue, in quanto i soggetti D variant, possono determinare nel ricevente RhD negativo la produzione di alloanticorpi . La corretta identificazione delle varianti dell’antigene RhD è fondamentale anche per le donne gravide RhD negative, in quanto vanno sottoposte ad immunoprofilassi se il neonato è un D variant e quindi può stimolare la produzione di anticorpi che potrebbero causare una malattia emolitica del neonato (MEN) in una successiva gravidanza con feto RhD positivo. Nei servizi trasfusionali (SIT) nasce quindi l’esigenza di dover correttamente tipizzare individui che, dai test sierologici, risultano negativi, in modo da determinare possibili D variant per evitare alloimmunizzazioni da trasfusione e programmare immunoprofilassi MEN nelle donne gravide quando richiesto

Work inclusion through supported employment? Perspectives of job counsellors in iceland

Funding Information: This study was conducted as part of the research project ‘Rethinking work inclusion for people with intellectual disabilities’ funded by the Research Council of Norway (‘HELSEVEL’ 2018–2020 number 273259). Publisher Copyright: © 2021 The Author(s).Supported employment (SE) programmes are generally considered an effective measure to support disabled people in the labour market. While research about SE has mostly focused on quantitative measures, such as successful placement, scholars have argued for scrutinising the meaning behind programme implementation. To understand how SE contributes to work inclusion of disabled people, we studied how job counsellors view their support and how they give meaning to their own roles and the roles of clients and employers. Qualitative interviews were conducted with 10 job counsellors within the SE programme of the Icelandic public employment service. Analysis of interview data shows that while participants attached general importance to inclusion, their day-to-day approach to client-centred support, relations with employers, and follow-up support reflected a social integration rather than an inclusion perspective. The policy context in which job counsellors implement the programme appeared to play an important role in shaping their approach to support.Peer reviewe

Child and parent perspectives of life quality of children with physical impairments compared with non-disabled peers

Publisher's version (útgefin grein).Background: Life quality has become a widely used concept within rehabilitation and occupational therapy practice. Aim: This study explored child and parent perspectives of life quality of children with physical impairments compared with a group of non-disabled children. Method: Data were collected with the Icelandic self- and proxy-reported versions of the KIDSCREEN-27. For children with physical impairments, reports from 34 children and 40 parents were included in the analyses, and in control group reports from 429 children and 450 parents were included. Results: Children with physical impairments evaluated their life quality within the average range on four out of five life quality dimensions. The lowest scores were within the physical well-being dimension. Self-reported scores of children with physical impairments were higher than those of their parents on all dimensions except autonomy and parent relations. Thus, the parents considered more environmental and personal factors to negatively influence their child’s life quality than children did themselves. Conclusion: Children with physical impairments experience their life quality similarly to non-disabled children. Significance: Focus on life quality can help occupational therapists to identify what circumstances positively or negatively influence client well-being and to focus more on contextual factors that contribute to disablement.We would like to thank the families who participated in the study. We would also like to thank Professor Barbara E Gibson at the University of Toronto who contributed to the research. The study was supported by the Icelandic Research Fund under Grant number 174299-051; and the Doctoral Grants of The University of Iceland Research Fund.Peer Reviewe

Cochlear Implant: the complexity involved in the decision making process by the family

El objetivo de esta investigación es comprender los significados atribuidos por la familia a las etapas del proceso de la toma de decisiones para el implante coclear en el hijo

Cellular and molecular mechanisms underpinning macrophage activation during remyelination

Remyelination is an example of central nervous system (CNS) regeneration, whereby myelin is restored around demyelinated axons, re-establishing saltatory conduction and trophic/metabolic support. In progressive multiple sclerosis, remyelination is limited or fails altogether which is considered to contribute to axonal damage/loss and consequent disability. Macrophages have critical roles in both CNS damage and regeneration, such as remyelination. This diverse range in functions reflects the ability of macrophages to acquire tissue microenvironment-specific activation states. This activation is dynamically regulated during efficient regeneration, with a switch from pro-inflammatory to inflammation-resolution/pro-regenerative phenotypes. Although, some molecules and pathways have been implicated in the dynamic activation of macrophages, such as NFκB, the cellular and molecular mechanisms underpinning plasticity of macrophage activation are unclear. Identifying mechanisms regulating macrophage activation to pro-regenerative phenotypes may lead to novel therapeutic strategies to promote remyelination in multiple sclerosis

A verification protocol for the probe sequences of Affymetrix genome arrays reveals high probe accuracy for studies in mouse, human and rat

BACKGROUND: The Affymetrix GeneChip technology uses multiple probes per gene to measure its expression level. Individual probe signals can vary widely, which hampers proper interpretation. This variation can be caused by probes that do not properly match their target gene or that match multiple genes. To determine the accuracy of Affymetrix arrays, we developed an extensive verification protocol, for mouse arrays incorporating the NCBI RefSeq, NCBI UniGene Unique, NIA Mouse Gene Index, and UCSC mouse genome databases. RESULTS: Applying this protocol to Affymetrix Mouse Genome arrays (the earlier U74Av2 and the newer 430 2.0 array), the number of sequence-verified probes with perfect matches was no less than 85% and 95%, respectively; and for 74% and 85% of the probe sets all probes were sequence verified. The latter percentages increased to 80% and 94% after discarding one or two unverifiable probes per probe set, and even further to 84% and 97% when, in addition, allowing for one or two mismatches between probe and target gene. Similar results were obtained for other mouse arrays, as well as for human and rat arrays. Based on these data, refined chip definition files for all arrays are provided online. Researchers can choose the version appropriate for their study to (re)analyze expression data. CONCLUSION: The accuracy of Affymetrix probe sequences is higher than previously reported, particularly on newer arrays. Yet, refined probe set definitions have clear effects on the detection of differentially expressed genes. We demonstrate that the interpretation of the results of Affymetrix arrays is improved when the new chip definition files are used

Dual role of striatal astrocytes in behavioral flexibility and metabolism in the context of obesity

Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior and are both dramatically altered in obesity, a multifactorial disease resulting from genetic and environmental factors. In both mice and human, exposure to calorie-dense food has been associated with increased astrocyte reactivity and pro-inflammatory response in the brain. Although our understanding of how astrocytes regulate brain circuits has recently flourish, whether and how striatal astrocytes contribute in regulating food-related behaviors and whole-body metabolism is still unknown. In this study, we show that exposure to enriched food leads to profound changes in neuronal activity and synchrony. Chemogenetic manipulation of astrocytes activity in the dorsal striatum was sufficient to restore the cognitive defect in flexible behaviors induced by obesity, while manipulation of astrocyte in the nucleus accumbens led to acute change in whole-body substrate utilization and energy expenditure. Altogether, this work reveals a yet unappreciated role for striatal astrocyte as a direct operator of reward-driven behavior and metabolic control

Features, Causes and Consequences of Splanchnic Sequestration of Amino Acid in Old Rats

RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging