RESUMO
The importance of remaining in, or re-entering, the labour market is emphasised by governments internationally. While this may bring benefits, progressive disabilities such as dementia affect an individual's employability. Although employers have legal obligations to support employees with disabilities, research suggests that employers are not providing this support to employees living with dementia and are undermining their capabilities. Drawing on interview data from 38 key informants collected over two studies, we explore the potential for supporting and promoting the employability of people living with dementia. A model of sustainable employability based on the Capability Approach is used as a lens to explore this issue. The findings demonstrate the implications of progressive disabilities for employability when the worker and their family are faced with dealing with a disability in a period of uncertainty with a lack of public and workplace understanding.
RESUMO
OBJECTIVES: As working lives extend and there is better recognition of early-onset dementias, employers need to consider dementia as a workplace concern. With suitable support, people living with dementia can continue employment - although, this is not appropriate for all. The requirement for employers to support employees living with dementia has human rights and legal foundations. This article considers whether employers consider dementia as a workplace concern; and the policies and/or practices available to support employees living with dementia. Thus, it develops understanding of whether employers are meeting their human rights/legislative obligations. METHOD: A sequential mixed-methods approach was employed, with data collection undertaken in Scotland (United Kingdom). An online survey was sent to employers across Scotland, with 331 participating. Thirty employer interviews were conducted, with the survey results informing the interview approach. RESULTS: The survey and interview data were analyzed separately and then combined and presented thematically. The themes identified were (1) Dementia as a workplace concern, (2) Support for employees living with dementia and (3) Employer policy development and awareness raising. The findings demonstrate dementia awareness, but this knowledge is not applied to employment situations. There was little evidence suggesting that the rights of employees living with dementia are consistently upheld. CONCLUSION: This research sends out strong messages about the rights and legal position of person living with dementia which cannot be ignored. The continuing potential of employees living with dementia and their legal rights are not consistently recognized. This highlights the need for robust training interventions for employers.
Assuntos
Demência , Local de Trabalho , Humanos , Escócia , Inquéritos e Questionários , Reino UnidoRESUMO
CONTEXT: Gordon Holmes syndrome (GHS) is characterized by cerebellar ataxia/atrophy and normosmic hypogonadotropic hypogonadism (nHH). The underlying pathophysiology of this combined neurodegeneration and nHH remains unknown. OBJECTIVE: We aimed to provide insight into the disease mechanism in GHS. METHODS: We studied a cohort of 6 multiplex families with GHS through autozygosity mapping and whole-exome sequencing. RESULTS: We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE), a lysophospholipase that maintains intracellular phospholipid homeostasis by converting lysophosphatidylcholine to glycerophosphocholine. Wild-type PNPLA6, but not PNPLA6 bearing these mutations, rescued a well-established Drosophila neurodegenerative phenotype caused by the absence of sws, the fly ortholog of mammalian PNPLA6. Inhibition of NTE activity in the LßT2 gonadotrope cell line diminished LH response to GnRH by reducing GnRH-stimulated LH exocytosis, without affecting GnRH receptor signaling or LHß synthesis. CONCLUSION: These results suggest that NTE-dependent alteration of phospholipid homeostasis in GHS causes both neurodegeneration and impaired LH release from pituitary gonadotropes, leading to nHH.
Assuntos
Ataxia Cerebelar/genética , Hormônio Liberador de Gonadotropina/deficiência , Hipogonadismo/genética , Degeneração Neural/genética , Fosfolipases/genética , Puberdade Tardia/genética , Adolescente , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Ataxia Cerebelar/metabolismo , Saúde da Família , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Homeostase/genética , Humanos , Hipogonadismo/metabolismo , Masculino , Pessoa de Meia-Idade , Degeneração Neural/metabolismo , Linhagem , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Puberdade Tardia/metabolismoRESUMO
loechrig (loe) mutant flies are characterized by progressive neuronal degeneration, behavioral deficits, and early death. The mutation is due to a P-element insertion in the gene for the γ-subunit of the trimeric AMP-activated protein kinase (AMPK) complex, whereby the insertion affects only one of several alternative transcripts encoding a unique neuronal isoform. AMPK is a cellular energy sensor that regulates a plethora of signaling pathways, including cholesterol and isoprenoid synthesis via its downstream target hydroxy-methylglutaryl (HMG)-CoA reductase. We recently showed that loe interferes with isoprenoid synthesis and increases the prenylation and thereby activation of RhoA. During development, RhoA plays an important role in neuronal outgrowth by activating a signaling cascade that regulates actin dynamics. Here we show that the effect of loe/AMPKγ on RhoA prenylation leads to a hyperactivation of this signaling pathway, causing increased phosphorylation of the actin depolymerizating factor cofilin and accumulation of filamentous actin. Furthermore, our results show that the resulting cytoskeletal changes in loe interfere with neuronal growth and disrupt axonal integrity. Surprisingly, these phenotypes were enhanced by expressing the Slingshot (SSH) phosphatase, which during development promotes actin depolymerization by dephosphorylating cofilin. However, our studies suggest that in the adult SSH promotes actin polymerization, supporting in vitro studies using human SSH1 that suggested that SSH can also stabilize and bundle filamentous actin. Together with the observed increase in SSH levels in the loe mutant, our experiments suggest that in mature neurons SSH may function as a stabilization factor for filamentous actin instead of promoting actin depolymerization.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Proteínas de Drosophila/metabolismo , Drosophila/genética , Mutação/genética , Neurônios/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Transdução de Sinais/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Actinas/metabolismo , Análise de Variância , Animais , Western Blotting , Sobrevivência Celular/fisiologia , Citoesqueleto/metabolismo , Drosophila/metabolismo , Feminino , Microscopia de Fluorescência , Polimerização , Prenilação de Proteína , Estabilidade Proteica , Transdução de Sinais/genéticaRESUMO
The Drosophila mutant loechrig (loe) shows age-dependent degeneration of the nervous system and is caused by the loss of a neuronal isoform of the AMP-activated protein kinase (AMPK) γ-subunit (also known as SNF4Aγ). The trimeric AMPK complex is activated by low energy levels and metabolic insults and regulates multiple important signal pathways that control cell metabolism. A well-known downstream target of AMPK is hydroxyl-methylglutaryl-CoA reductase (HMGR), a key enzyme in isoprenoid synthesis, and we have previously shown that HMGR genetically interacts with loe and affects the severity of the degenerative phenotype. Prenylation of proteins like small G-proteins is an important posttranslational modification providing lipid moieties that allow the association of these proteins with membranes, thereby facilitating their subsequent activation. Rho proteins have been extensively studied in neuronal outgrowth, however, much less is known about their function in neuronal maintenance. Here we show that the loe mutation interferes with isoprenoid synthesis, leading to increased prenylation of the small GTPase Rho1, the fly orthologue of vertebrate RhoA. We also demonstrate that increased prenylation and Rho1 activity causes neurodegeneration and aggravates the behavioral and degenerative phenotypes of loe. Because we cannot detect defects in the development of the central nervous system in loe, this suggests that loe only interferes with the function of the RhoA pathway in maintaining neuronal integrity during adulthood. In addition, our results show that alterations in isoprenoids can result in progressive neurodegeneration, supporting findings in vertebrates that prenylation may play a role in neurodegenerative diseases like Alzheimer's Disease.
Assuntos
Drosophila/genética , Mutação , Sistema Nervoso/patologia , Prenilação de Proteína , Proteína rhoA de Ligação ao GTP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Hidroximetilglutaril-CoA Redutases/genéticaRESUMO
The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70-90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested.
Assuntos
Golfinhos/fisiologia , Ecolocação/fisiologia , Perda Auditiva/fisiopatologia , Baleias/fisiologia , Fatores Etários , Animais , Audiometria/métodos , Golfinhos/classificação , Feminino , Humanos , Masculino , Especificidade da Espécie , Baleias/classificaçãoRESUMO
Several mass strandings of beaked whales have recently been correlated with military exercises involving mid-frequency sonar highlighting unknowns regarding hearing sensitivity in these species. We report the hearing abilities of a stranded juvenile beaked whale (Mesoplodon europaeus) measured with auditory evoked potentials. The beaked whale's modulation rate transfer function (MRTF) measured with a 40-kHz carrier showed responses up to an 1,800 Hz amplitude modulation (AM) rate. The MRTF was strongest at the 1,000 and 1,200 Hz AM rates. The envelope following response (EFR) input-output functions were non-linear. The beaked whale was most sensitive to high frequency signals between 40 and 80 kHz, but produced smaller evoked potentials to 5 kHz, the lowest frequency tested. The beaked whale hearing range and sensitivity are similar to other odontocetes that have been measured.
Assuntos
Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos/fisiologia , Percepção da Altura Sonora/fisiologia , Baleias/fisiologia , Estimulação Acústica , Animais , Análise de Fourier , Arcada Osseodentária/fisiologia , MasculinoRESUMO
Auditory evoked potential (AEP) measurements of two Florida manatees (Trichechus manatus latirostris) were measured in response to amplitude modulated tones. The AEP measurements showed weak responses to test stimuli from 4 kHz to 40 kHz. The manatee modulation rate transfer function (MRTF) is maximally sensitive to 150 and 600 Hz amplitude modulation (AM) rates. The 600 Hz AM rate is midway between the AM sensitivities of terrestrial mammals (chinchillas, gerbils, and humans) (80-150 Hz) and dolphins (1,000-1,200 Hz). Audiograms estimated from the input-output functions of the EPs greatly underestimate behavioral hearing thresholds measured in two other manatees. This underestimation is probably due to the electrodes being located several centimeters from the brain.
Assuntos
Audição/fisiologia , Trichechus/fisiologia , Estimulação Acústica , Animais , Limiar Auditivo/fisiologia , Condicionamento Operante , Eletrodos Implantados , Potenciais Evocados Auditivos/fisiologia , Alimentos , Masculino , Recompensa , Fatores de TempoRESUMO
Data from behavioural observations and acoustic recordings of free-ranging bottlenose dolphins (Tursiops truncatus) were analysed to determine whether signature whistles are produced by wild undisturbed dolphins, and how whistle production varies with activity and group size. The study animals were part of a resident community of bottlenose dolphins near Sarasota, Florida, USA. This community of dolphins provides a unique opportunity for the study of signature-whistle production, since most animals have been recorded during capture-release events since 1975. Three mother-calf pairs and their associates were recorded for a total of 141.25 h between May and August of 1994 and 1995. Whistles of undisturbed dolphins were compared with those recorded from the same individuals during capture-release events. Whistles were conservatively classified into one of four categories: signature, probable signature, upsweep or other. For statistical analyses, signature and probable signature whistles were combined into a 'signature' category; upsweep and other whistles were combined into a 'non-signature' category. Both 'signature' and 'non-signature' whistle frequencies significantly increased as group size increased. There were significant differences in whistle frequencies across activity types: both 'signature' and 'non-signature' whistles were most likely to occur during socializing and least likely to occur during travelling. There were no significant interactions between group size and activity type. Signature and probable signature whistles made up ca. 52% of all whistles produced by these free-ranging bottlenose dolphins.