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Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III and VII are associated with lysosomal accumulation of heparan sulphate and manifest with neurological deterioration. Most of these neurological MPS currently lack effective treatments. Here, we report that, compared to controls, neuraminidase 1 (NEU1) activity is drastically reduced in brain tissues of neurological MPS patients and in mouse models of MPS I, II, IIIA, IIIB and IIIC, but not of other neurological lysosomal disorders not presenting with heparan sulphate storage. We further show that accumulated heparan sulphate disrupts the lysosomal multienzyme complex of NEU1 with cathepsin A (CTSA), ß-galactosidase (GLB1) and glucosamine-6-sulfate sulfatase (GALNS) necessary to maintain enzyme activity, and that NEU1 deficiency is linked to partial deficiencies of GLB1 and GALNS in cortical tissues and iPSC-derived cortical neurons of neurological MPS patients. Increased sialylation of N-linked glycans in brain samples of human MPS III patients and MPS IIIC mice implicated insufficient processing of brain N-linked sialylated glycans, except for polysialic acid, which was reduced in the brains of MPS IIIC mice. Correction of NEU1 activity in MPS IIIC mice by lentiviral gene transfer ameliorated previously identified hallmarks of the disease, including memory impairment, behavioural traits, and reduced levels of the excitatory synapse markers VGLUT1 and PSD95. Overexpression of NEU1 also restored levels of VGLUT1-/PSD95-positive puncta in cortical neurons derived from iPSC of an MPS IIIA patient. Together, our data demonstrate that heparan sulphate-induced secondary NEU1 deficiency and aberrant sialylation of glycoproteins implicated in synaptogenesis, memory, and behaviour constitute a novel pathological pathway in neurological MPS spectrum crucially contributing to CNS pathology.
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BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.
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Cuidadores , Servicios de Atención de Salud a Domicilio , Humanos , Calidad de Vida , Cuidados Paliativos/métodosRESUMEN
Mutations in ASAH1 have been linked to two allegedly distinct disorders: Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). We have previously reported FD-like phenotypes in mice harboring a single amino acid substitution in acid ceramidase (ACDase), P361R, known to be pathogenic in humans (P361R-Farber). Here we describe a mouse model with an SMA-PME-like phenotype (P361R-SMA). P361R-SMA mice live 2-3-times longer than P361R-Farber mice and have different phenotypes including progressive ataxia and bladder dysfunction, which suggests neurological dysfunction. We found profound demyelination, loss of axons, and altered sphingolipid levels in P361R-SMA spinal cords; severe pathology was restricted to the white matter. Our model can serve as a tool to study the pathological effects of ACDase deficiency on the central nervous system and to evaluate potential therapies for SMA-PME.
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Lipogranulomatosis de Farber , Atrofia Muscular Espinal , Epilepsias Mioclónicas Progresivas , Humanos , Ratones , Animales , Lipogranulomatosis de Farber/genética , Lipogranulomatosis de Farber/metabolismo , Lipogranulomatosis de Farber/patología , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patología , Esfingolípidos/metabolismo , Epilepsias Mioclónicas Progresivas/genética , Epilepsias Mioclónicas Progresivas/patología , FenotipoRESUMEN
Purpose: To explore the death experiences of nursing students in their personal lives. Methods: This study employed a qualitative descriptive design using the semi-structured interview approach. A purposive sampling method was used to recruit 24 nursing students from September 2020 to July 2022. Data were analyzed using Colaizzi's analysis method. Lincoln and Guba's criteria was used to evaluate the trustworthiness of the data. Results: Four main themes emerged from the interviews: (a) reactions to encounters with death; (b) adjustment strategies; (c) personal growth induced by the death experiences; and (d) professional reflections for preparing nurse role. Conclusions: Although the death of a loved one makes nursing students suffer from grief and emotional distress, we show that the experience promotes the personal growth and professional competencies of nursing students and thereby, developing their overall aptitude towards the profession. Death experiences of nursing students have shown to allow them to reflect on both life and death, to consider the demands of the nursing profession, and to provide foundation for nursing students to be more empathetic and compassionate when facing death in the future. Exploring death experiences of nursing students is vital in better providing better quality education and personal support for nursing students.
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BACKGROUND: Effective communication between people with advanced cancer and their family members on end-of-life issues has a profound impact on meeting needs and improving quality of life of both sides. Several studies have shown that patient-family end-of-life communication is not always adequate and optimal. Little is known about the experiences of end-of-life communication within families of people with advanced cancer in China. OBJECTIVES: The aim of this study was to explore the experiences of end-of-life communication between people with advanced cancer and their family members in China and the factors influencing their communication. DESIGN: A qualitative descriptive study using semi-structured interviews was conducted. SETTINGS: This study took place at three tertiary hospitals in Beijing, China from July 2018 to October 2019. PARTICIPANTS: Purposive sampling was employed to select participants. Eleven people with advanced cancer and 14 family members were finally interviewed. METHODS: Audio-recordings were transcribed verbatim and entered into qualitative data analysis software. Qualitative data were analyzed using a content analysis approach. RESULTS: Five themes and associated categories were identified: (1) silence without intention; (2) silence with intention; (3) silence-breaking; (4) openness without restraint; and (5) the influencing factors of end-of-life communication. These four states of end-of-life communication have different essential characteristics and change under the influence of the awareness of disease diagnosis, awareness and acceptance of the incurability of disease, and fear of impending death. CONCLUSIONS: Affected by the willingness and ability to communicate about end-of-life issues, people with advanced cancer and their family members present four communication states, namely silence without intention, silence with intention, silence-breaking, and openness without restraint. The study provides an insight into end-of-life communication experiences within families where different communication states are interconnected. The findings enable professionals to evaluate the communication and its influencing factors, so as to provide feasible and effective end-of-life communication support. REGISTRATION: Not registered.
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Neoplasias , Calidad de Vida , China , Comunicación , Muerte , Familia , Humanos , Investigación CualitativaRESUMEN
The majority of mucopolysaccharidosis IIIC (MPS IIIC) patients have missense variants causing misfolding of heparan sulfate acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), which are potentially treatable with pharmacological chaperones. To test this approach, we generated a novel HgsnatP304L mouse model expressing misfolded HGSNAT Pro304Leu variant. HgsnatP304L mice present deficits in short-term and working/spatial memory 2-4 mo earlier than previously described constitutive knockout Hgsnat-Geo mice. HgsnatP304L mice also show augmented severity of neuroimmune response, synaptic deficits, and neuronal storage of misfolded proteins and gangliosides compared with Hgsnat-Geo mice. Expression of misfolded human Pro311Leu HGSNAT protein in cultured hippocampal Hgsnat-Geo neurons further reduced levels of synaptic proteins. Memory deficits and majority of brain pathology were rescued in mice receiving HGSNAT chaperone, glucosamine. Our data for the first time demonstrate dominant-negative effects of misfolded HGSNAT Pro304Leu variant and show that they are treatable by oral administration of glucosamine. This suggests that patients affected with mutations preventing normal folding of the enzyme can benefit from chaperone therapy.
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Mucopolisacaridosis , Mucopolisacaridosis III , Acetiltransferasas , Animales , Glucosamina , Heparitina Sulfato , Humanos , Ratones , Ratones Noqueados , Mucopolisacaridosis III/genética , Mucopolisacaridosis III/patologíaRESUMEN
BACKGROUND: Caring is an essential component of professional nursing practice, which directly affects the quality of patient care. Nurses' caring ability may not meet patients' demands for high-quality care. There are challenges in designing and implementing interventions to improve nurses' caring ability, especially in China. Understanding Chinese nurses' caring ability and related influential factors serves as the basis for effective interventions to improve their ability to care for patients. AIM: To describe the caring ability of nurses and its potential predictors in China. METHODS: From January to February 2018, a cross-sectional survey was conducted among 2304 Registered Nurses working at different levels of hospitals across 29 provinces in China. The structured online survey included socio-demographic information, Caring Ability Inventory, Caring Efficacy Scale and Professional Quality of Life. Descriptive statistics, univariate analyses and multivariate analyses were conducted. RESULTS: Overall caring ability and its three dimensions of the participants were all significantly lower than the Nkongho' norm, an international scoring standard of nurse's caring ability. Age, employment type, workplace, caring efficacy, compassion satisfaction, burnout and secondary traumatic stress were predictors of knowing, explaining 41.8% of the variance. Predictors of courage were educational level, bereavement experience, caring efficacy, compassion satisfaction and burnout (31.7% of the variance). Educational level, workplace, exposure to critically ill patients, caring efficacy, compassion satisfaction, burnout and secondary traumatic stress were influencing factors of patience, accounting for 19.5% of the variance. CONCLUSIONS: Chinese nurses' caring ability, with patience, knowing, and courage in descending order. Particular attention needs to be paid to the courage dimension of the nurses' caring ability. Further, the predictors of overall caring ability and each dimension were diverse. These results indicate that nurse educators and administrators need to identify training priorities and design targeted interventions based on the influencing factors.
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Enfermeras y Enfermeros , Calidad de Vida , China , Estudios Transversales , Humanos , Satisfacción en el TrabajoRESUMEN
AIMS AND OBJECTIVES: To examine the understanding of caring in the practice of community nursing from the perspectives of patients and nurses. BACKGROUND: An increasing population of patients with chronic disease has produced a need for humanistic caring in communities. As a result, caring has become a core value of community nursing professionals. However, community nurses meet many difficulties in trying to practice person-centred care with their clients. Furthermore, most community nurses-especially in China-lack systematic education and training about caring because the practical meaning of caring in community practice is unknown. DESIGN: The qualitative study described herein employed inductive content analysis. METHODS: Eleven community patients with chronic disease and fifteen community nurses who were nominated as a caring nurse from different community clinics in Beijing, China, participated in thirty-one interviews during January to August in 2018. Nine documents from the interviewed nurses were collected. Both interview data and documents were analysed using strategies of inductive content analysis. The COREQ checklist was used. RESULTS: Patients and their corresponding nurses described a wide range of caring experiences that were generalised into 28 concepts. Caring emerged as an inter-dynamic system that comprised the foundation and quality of a caring relationship, the caring philosophy and behaviours of interactions, and positive feedback from caring interactions. A relationship-based framework of caring in community nursing practice was constructed. CONCLUSIONS: Identifying this systematic concept of caring provides insights that are applicable to the creation of targeted management, education and practice interventions to ultimately enhance the quality of community health care-in China or elsewhere. RELEVANCE TO CLINICAL PRACTICE: The systematic understanding of caring in community nursing practice will inform nurses in community health clinics, their educators and their managers on how to provide care to community patients and how to develop caring competence for community nurses.