RESUMEN
Aim: Although the US FDA encourages manufacturers of medical devices to submit real-world evidence (RWE) to support regulatory decisions, the ability of real-world data (RWD) to generate evidence suitable for decision making remains unclear. The 2017 Medical Device User Fee Amendments (MDUFA IV), authorized the National Evaluation System for health Technology Coordinating Center (NESTcc) to conduct pilot projects, or 'Test-Cases', to assess whether current RWD captures the information needed to answer research questions proposed by industry stakeholders. We synthesized key lessons about the challenges conducting research with RWD and the strategies used by research teams to enhance their ability to generate evidence from RWD based on 18 Test-Cases conducted between 2020 and 2022. Materials & methods: We reviewed study protocols and reports from each Test-Case team and conducted 49 semi-structured interviews with representatives of participating organizations. Interview transcripts were coded and thematically analyzed. Results: Challenges that stakeholders encountered in working with RWD included the lack of unique device identifiers, capturing key data elements and their appropriate meaning in structured data, limited reliability of diagnosis and procedure codes in structured data, extracting information from unstructured electronic health record (EHR) data, limited capture of long-term study end points, missing data and data sharing. Successful strategies included using manufacturer and supply chain data, leveraging clinical registries and registry reporting processes to collect and aggregate data, querying standardized EHR data, implementing natural language processing algorithms and using multidisciplinary research teams. Conclusion: The Test-Cases identified numerous challenges working with RWD but also opportunities to address these challenges and improve researchers' ability to use RWD to generate evidence on medical devices.
RESUMEN
Osseointegration implant (OI) surgery is the latest rehabilitation technology for amputees, where a bone-anchored implant obviates the limitations of traditional socket prostheses. The bone mineral density (BMD) in the periprosthetic and other anatomical regions can be used to assess bone remodelling following OI surgery. Currently, limited studies have used BMD measurements in reporting post-operative OI outcomes and the association between the maintenance of BMD and implant efficacy has remained elusive. This review captured and analysed all studies that have reported the BMD as an objective outcome measure in patients with trans-femoral or trans-tibial OI. The PubMed, Medline, Scopus and Web of Science databases were searched using the terms 'amputation', 'osseointegration' and 'bone mineral density'. A total of 6 studies involving human participants were included for analysis. All studies used dual X-ray absorptiometry and/or X-rays for measuring BMD. Rehabilitation of trans-femoral or trans-tibial amputation using OI may help restore healthy BMD by enabling physiological bone loading. However, there is a low correlation between the BMD around the OI and the success of OI surgery or the risk of periprosthetic fractures. This review summarises the current evidence on BMD assessment in OI for lower limb amputee rehabilitation. Despite the great variability in the results, the available evidence suggests that OI may help restore BMD following surgery. The limited evidence calls for further investigation, as well as the development of a standard BMD measurement protocol.
RESUMEN
BACKGROUND: Some reports point to dietary caffeine intake as a cause of increased plasma clozapine concentrations in certain patients. METHODS: We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in relation to reported (i) coffee (caffeine) and (ii) chocolate (caffeine and theobromine) intake in samples submitted for clozapine therapeutic drug monitoring, 1993-2017. RESULTS: There was information on coffee ingestion for 16,558 samples (8833 patients) from males and 5886 samples (3433 patients) from females and on chocolate ingestion for 12,616 samples (7568 patients) from males and 4677 samples (2939 patients) from females. When smoking was considered, there was no discernible effect of either coffee or chocolate ingestion either on the median dose of clozapine or on the median plasma clozapine and norclozapine concentrations in men and in women. However, cigarette smoking was associated with higher coffee and chocolate consumption. Although male nonsmokers who reported drinking 3 or more cups of coffee daily had significantly higher median plasma clozapine and norclozapine concentrations than those who drank less coffee, they were also prescribed a significantly higher clozapine dose. There was no clear effect of coffee ingestion on plasma clozapine and norclozapine in female nonsmokers. IMPLICATIONS: Inhibition of clozapine metabolism by caffeine at the doses of caffeine normally encountered in those treated with clozapine is unlikely even in male nonsmokers. Measurement of plasma caffeine in an appropriate sample should be considered in any future investigation into a presumed clozapine-caffeine interaction.
Asunto(s)
Chocolate , Clozapina/análogos & derivados , Femenino , Humanos , Masculino , Café , CafeínaRESUMEN
AIM: End-stage kidney disease (ESKD) is increasingly becoming a healthcare concern in New Zealand and haemodialysis remains the most common modality of treatment. Frailty and health-related quality of life (HRQOL) are established predictors of prognosis and have already been shown to be poor in the dialyzing population. Existing data show correlation between these measures in the ESKD population, however there is little evidence for those on haemodialysis specifically. Our study aimed to assess for a correlation between frailty and HRQOL in the haemodialysis population at Palmerston North Hospital, and to assess for any differences in frailty and HRQOL scores between indigenous Maori and non-Maori subgroups. METHODS: A cross-sectional study was conducted involving 93 in-centre haemodialysis patients from Palmerston North Hospital, New Zealand. Baseline demographic data was measured alongside frailty and HRQOL scores, which were measured using the Kidney Disease Quality of Life tool (KDQOL-36) and the Edmonton Frail Scale. RESULTS: A statistically significant negative correlation was observed between frailty and all aspects of HRQOL (p < .05), with the strongest correlation observed between frailty and the physical component (r = -.64, p = <.001). Independent samples t-test showed no statistically significant difference between scores for Maori and non-Maori in frailty (M = 7.4, SD = 3.3 vs. M = 6.8, SD = 3.2; t (91) = -0.92, p = .80), or HRQOL (p values > .05 in all components). CONCLUSION: A negative correlation was observed between frailty and HRQOL. This information can be beneficial in guiding discussions around treatment modality and for future patients and useful in enabling better predictions of prognosis. No statistically significant differences in frailty and HRQOL scores were observed between Maori and non-Maori groups, however the generalizability of this finding is limited due to the insufficient size of the study population.
Asunto(s)
Fragilidad , Fallo Renal Crónico , Humanos , Calidad de Vida , Fragilidad/diagnóstico , Fragilidad/epidemiología , Pueblo Maorí , Nueva Zelanda/epidemiología , Estudios Transversales , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , HospitalesRESUMEN
BACKGROUND: Technology can improve care delivery, patient outcomes, and staff satisfaction, but integration into the clinical workflow remains challenging. To contribute to this knowledge area, this study examined the implementation continuum of a contact-free, continuous monitoring system (CFCM) in an inpatient setting. CFCM monitors vital signs and uses the information to alert clinicians of important changes, enabling early detection of patient deterioration. METHODS: Data were collected throughout the entire implementation continuum at a community teaching hospital. Throughout the study, 3 group and 24 individual interviews and five process observations were conducted. Postimplementation alarm response data were collected. Analysis was conducted using triangulation of information sources and two-coder consensus. RESULTS: Preimplementation perceived barriers were alarm fatigue, questions about accuracy and trust, impact on patient experience, and challenges to the status quo. Stakeholders identified the value of CFCM as preventing deterioration and benefitting patients who are not good candidates for telemetry. Educational materials addressed each barrier and emphasized the shared CFCM values. Mean alarm response times were below the desired target of two minutes. Postimplementation interview analysis themes revealed lessened concerns of alarm fatigue and improved trust in CFCM than anticipated. Postimplementation challenges included insufficient training for secondary users and impact on patient experience. CONCLUSION: In addition to understanding the preimplementation anticipated barriers to implementation and establishing shared value before implementation, future recommendations include studying strategies for optimal tailoring of education to each user group, identifying and reinforcing positive process changes after implementation, and including patient experience as the overarching element in frameworks for digital tool implementation.
Asunto(s)
Fatiga de Alerta del Personal de Salud , Atención a la Salud , Femenino , Humanos , Investigación Cualitativa , Hospitales de Enseñanza , Monitoreo FisiológicoRESUMEN
There is evidence that men's testosterone levels decline across the transition to fatherhood and that this decline may reflect fathers' investment in the new family. There is also emerging evidence that cohabiting couples show synchrony or within-couple associations in testosterone levels during the perinatal period. Hormonal synchrony may act as a mechanism that supports fathers' biological preparation for parenthood, perhaps by facilitating perinatal declines in paternal testosterone. However, few studies have examined testosterone synchrony and change within couples. A sample of 97 U.S. couples expecting their first child provided testosterone samples during pregnancy, and of those couples, 78 couples also provided testosterone at seven months postpartum. Couples reported on relationship satisfaction both at prenatal and postpartum visits. Bayesian multilevel modeling revealed within-couple testosterone synchrony both during pregnancy and postpartum. Testosterone synchrony during pregnancy predicted a greater drop in fathers' testosterone levels from prenatal to postpartum and higher paternal postpartum relationship quality. Fathers' lower prenatal testosterone levels also subsequently predicted higher self-reported postpartum relationship quality for both parents. In sum, this study finds that couples' testosterone levels show synchrony across the transition to parenthood in ways that are associated with couple relationship quality and men's neuroendocrine preparation for fatherhood.
Asunto(s)
Padres , Testosterona , Masculino , Embarazo , Femenino , Niño , Humanos , Teorema de Bayes , Periodo Posparto , Padre , Madres , Responsabilidad ParentalRESUMEN
Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described. Methods: A cross-sectional survey was sent to women from ADTKD families. Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls (p = 0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls (p < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals (p = 0.06). Only 12% of babies required a neonatal intensive care unit stay. Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes.
RESUMEN
Previously we identified that biomedical science students commonly misunderstand "creativity," mistaking it for "freedom." In the present study, we describe and evaluate a workshop designed to increase students' awareness of creativity as a highly sought-after employability skill and cognitive process applicable to scientific endeavors. To achieve this, we developed and introduced students to a process called the "Diamond Model," utilizing a case study to contextualize and signpost the creative processes of divergent and convergent thinking. This model was introduced to students in the first workshop of a 12-week undergraduate biochemistry unit (subject) within the Bachelor of Biomedical Science at Monash University, Australia. Students completed pre- and post-workshop surveys to gauge the impact of the workshop on their conceptions of creativity and Bloom's taxonomy of learning. In addition, reflective journals were completed by a small subset of students (n = 9) following the workshop. Following the workshop, over 65% of students indicated that their conception of creativity had changed. Thematic analysis of students' survey responses and reflections indicated that this change in the conception of creativity included broadening their definition of creativity, increased awareness of creativity as a skill and science as a creative process, and that creativity can be applied to different areas of life. Students attributed the signposting of creative elements as a contributing factor to their increased awareness. These results indicate the positive impact the workshop and our novel Diamond model had on student conception of creativity, highlighting the importance of explicit communication and signposting in skill development.
Asunto(s)
Creatividad , Estudiantes , Humanos , Estudiantes/psicología , Aprendizaje , Universidades , DiamanteRESUMEN
Three-dimensional printing (3DP) is a popular manufacturing technique with versatile potential for materials processing in tissue engineering and regenerative medicine. In particular, the repair and regeneration of significant bone defects remain as substantial clinical challenges that require biomaterial implants to maintain mechanical strength and porosity, which may be realized using 3DP. The rapid progress in 3DP development in the past decade warrants a bibliometric analysis to gain insights into its applications in bone tissue engineering (BTE). Here, we performed a comparative study using bibliometric methods for 3DP in bone repair and regeneration. A total of 2,025 articles were included, and the results showed an increase in the number of publications and relative research interest on 3DP annually worldwide. China was the leader in international cooperation in this field and also the largest contributor to the number of citations. The majority of articles in this field were published in the journal Biofabrication. Chen Y was the author who made the highest contribution to the included studies. The keywords included in the publications were mainly related to BTE and regenerative medicine (including "3DP techniques," "3DP materials," "bone regeneration strategies," and "bone disease therapeutics") for bone regeneration and repair. This bibliometric and visualized analysis provides significant insights into the historical development of 3DP in BTE from 2012 to 2022, which will be beneficial for scientists to conduct further investigations into this dynamic field.
RESUMEN
This cross-sectional study aimed to explore various determinants of future physical activity (PA) participation in adolescents across sociodemographic groups. Sociodemographic characteristics (age, gender, ethnicity, deprivation status, physical disability status) were assessed in a national sample (n = 6906) of adolescents (12-17 years old) between 2017 and 2020 in New Zealand. The determinants of future PA participation chosen for analysis included current indicators of PA participation (i.e., total time, number of types, number of settings). We also examined widely recognised modifiable intrapersonal (i.e., physical literacy) and interpersonal (i.e., social support) determinants of current and future PA behaviour, along with indicators of PA availability issues. Older adolescents scored worse across all determinants of future PA than younger adolescents, with a key transition point appearing at 14-15 years of age. Maori and Pacific ethnicities scored best across each determinant category on average, with Asian populations scoring the worst. Gender diverse adolescents scored substantially worse than male and female adolescents across every determinant. Physically disabled adolescents scored worse than non-disabled across all determinants. Adolescents from medium and high deprivation neighbourhoods scored similarly across most determinants of future PA participation and both tended to score worse than people from low deprivation neighbourhoods. A particular focus on the improvement of future PA determinants is warranted within adolescents who are older, Asian, gender diverse, physically disabled, and from medium to high deprivation neighbourhoods. Future investigation should prioritise the longitudinal tracking of PA behaviours over time and develop interventions that affect multiple future PA determinants across a range of sociodemographic backgrounds.
Asunto(s)
Ejercicio Físico , Pueblo Maorí , Adolescente , Femenino , Humanos , Masculino , Estudios Transversales , Actividad Motora , Nueva Zelanda , NiñoRESUMEN
Latent variable models can create a latent dementia index (LDI) using cognitive and functional ability to approximate dementia likelihood. The LDI approach has been applied across diverse cohorts. It is unclear whether sex affects its measurement properties. We use Wave A (2001-2003) of the Aging, Demographics, and Memory Study (n = 856). Multiple group confirmatory factor analysis (CFA) was used to test measurement invariance (MI) using informant-reported functional ability and cognitive performance tasks, which we group into verbal, nonverbal, and memory. Partial scalar invariance was found, allowing for testing sex differences in LDI means (MDiff = 0.38). The LDI correlated with consensus panel dementia diagnosis, Mini-Mental State Examination (MMSE), and dementia risk factors (low education, advanced age, and apolipoprotein ε4 [APOE-ε4] status) for men and women. The LDI validly captures dementia likelihood to permit estimation of sex differences. LDI sex differences indicate higher dementia likelihood in women, potentially due to social, environmental, and biological factors.
RESUMEN
WHAT IS KNOWN ON THE SUBJECT: Police and ambulance staff are increasingly asked to help people experiencing mental health crises, but they often feel under-prepared. The single frontline service approach is time-intensive and risks a coercive pathway to care. The emergency department is the default location for transfers by police or ambulance involving a person involved in a mental health crisis, despite being viewed as suboptimal. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Police and ambulance staff struggled keeping up with the mental health demand, reporting inadequate mental health training, little enjoyment and negative experiences when trying to access help from other services. Most mental health staff had adequate mental health training and enjoyed their work, but many experienced difficulties getting help from other services. Police and ambulance staff found it hard to work with mental health services. WHAT ARE THE IMPLICATIONS FOR PRACTICE: The combination of limited training, poor interagency referral processes, and difficulties accessing support from mental health services means that when police and ambulance services attend mental health crises alone, distress may be heightened and prolonged. Enhanced mental health training for first responders and more streamlined referral processes may improve process and outcomes. Mental health nurses have key skills that could be utilized in assisting police and ambulance staff who attend 911 emergency mental health calls. New models such as co-response teams, whereby police, mental health clinicians and ambulance staff respond conjointly should be trialled and evaluated. ABSTRACT: INTRODUCTION: First responders are increasingly called to assist people experiencing mental health crises but little research exists canvassing multi-agency perspectives of such work. AIM/QUESTION: To understand the views of police officers, ambulance and mental health staff attending mental health or suicide-related crises in Aotearoa New Zealand and to discover how they experience current models of cross-agency collaboration. METHODS: A descriptive cross-sectional survey involving mixed methods. Quantitative data were analysed using descriptive statistics and free text by content analysis. RESULTS: Participants included 57 police officers, 29 paramedics and 33 mental health professionals. Mental health staff felt adequately trained, but only 36% described good processes for accessing inter-agency support. Police and ambulance staff felt undertrained and unprepared. Accessing mental health expertise was considered difficult by 89% of police and 62% of ambulance staff. DISCUSSION: Frontline services struggle managing mental health-related 911 emergencies. Current models are not working well. Miscommunication, dissatisfaction and distrust exist between police, ambulance and mental health services. CONCLUSION: The single-agency frontline response may be detrimental to service users in crisis and under-utilizes the skills of mental health staff. New ways of inter-agency cooperation are required, such as co-located police, ambulance and mental health nurses responding in partnership.
Asunto(s)
Servicios de Salud Mental , Salud Mental , Humanos , Policia , Estudios Transversales , ParamédicoRESUMEN
OBJECTIVE: Mental health-related calls to emergency services made via 111 (New Zealand) or 000 (Australia) often represent critical junctures for the person in crisis. Traditionally, police, ambulance and mental health services work separately to manage such emergencies. Sequential agency responses may be protracted and cause escalation. This study tests multi-agency co-response aiming for more integrated, faster, safer and less coercive management of mental health crises. METHODS: Immediate and 1-month outcomes of mental health emergency calls made to police and ambulance were compared according to whether they occurred on days with co-response availability. Outcomes measured included emergency department admission and waiting times, psychiatric admissions, compulsory treatment, use of force, detention in police cells and the time to resolution of the event. Relative risk estimates were constructed. RESULTS: A total 1273 eligible mental health emergency callouts occurred between March 2020 and March 2021 (38% coded 'mental health' emergencies, 48% suicide risk and 14% as 'other'), 881 on days with co-response availability and 392 on days without. Co-response interventions were resolved faster and were more likely to be community-based. Fewer than one-third (32%) led to emergency department admissions, compared with close to half (45%) on days without co-response (risk ratio: 0.7 [0.6, 0.8]). In the following month, the number of emergency department and mental health admissions reduced (p < 0.01 and 0.05, respectively). There were no statistically significant differences in use of force and few people were detained in police custody. CONCLUSION: Co-response intervention increased the likelihood of mental health crises being resolved in the community and reduced hospitalisations. Benefits were sustained at 1 month.
Asunto(s)
Trastornos Mentales , Suicidio , Humanos , Ambulancias , Urgencias Médicas , Policia , Salud Mental , Trastornos Mentales/terapiaRESUMEN
OBJECTIVE: To identify barriers and facilitators to the use of formal dementia services among underserved and minority groups (UMG) in the United States and Germany. METHOD: Semi-structured qualitative interviews with caregivers (N = 18) of persons with dementia in the United States and Germany. Data were analyzed using thematic analysis. RESULTS: Caregivers described their experiences in three stages of seeking, initiating, and utilizing care, and different factors served to hinder or enable the use of care services in each stage. The most important factors included limited knowledge about dementia, challenges interacting with healthcare systems, and how closely formal services met the expectations and needs of caregivers, particularly with regard to accommodating cultural or ethnic/racial identity. Caregivers preferred interacting with service care providers who shared a similar identity to receive information or services. CONCLUSION: Barriers and facilitators to using dementia care services vary by stage of engaging services and may be shared across different healthcare contexts. Targeting specific barriers and strengthening facilitators could help reduce disparities in dementia care among UMG.
Asunto(s)
Demencia , Grupos Minoritarios , Humanos , Demencia/terapia , Investigación Cualitativa , Cuidadores , Alemania , Poblaciones Minoritarias, Vulnerables y Desiguales en SaludRESUMEN
The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges.
RESUMEN
Deep neural networks (DNNs) show promise in image-based medical diagnosis, but cannot be fully trusted since they can fail for reasons unrelated to underlying pathology. Humans are less likely to make such superficial mistakes, since they use features that are grounded on medical science. It is therefore important to know whether DNNs use different features than humans. Towards this end, we propose a framework for comparing human and machine perception in medical diagnosis. We frame the comparison in terms of perturbation robustness, and mitigate Simpson's paradox by performing a subgroup analysis. The framework is demonstrated with a case study in breast cancer screening, where we separately analyze microcalcifications and soft tissue lesions. While it is inconclusive whether humans and DNNs use different features to detect microcalcifications, we find that for soft tissue lesions, DNNs rely on high frequency components ignored by radiologists. Moreover, these features are located outside of the region of the images found most suspicious by radiologists. This difference between humans and machines was only visible through subgroup analysis, which highlights the importance of incorporating medical domain knowledge into the comparison.
Asunto(s)
Neoplasias de la Mama , Calcinosis , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Redes Neurales de la Computación , Percepción , RadiólogosRESUMEN
OBJECTIVES: To enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers' challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use. METHODS: We conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis. RESULTS: Accessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE. CONCLUSIONS: Technical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE.
Asunto(s)
Aprobación de Recursos , Evaluación de la Tecnología Biomédica , United States Food and Drug Administration , Entrevistas como Asunto , Estados UnidosRESUMEN
Although several studies have shown small longitudinal associations between baseline loneliness and subsequent dementia risk, studies rarely test whether change in loneliness predicts dementia risk. Furthermore, as both increase with advancing age, genetic and environmental selection processes may confound the putative causal association between loneliness and dementia risk. We used a sample of 2,476 individual twins from three longitudinal twin studies of aging in the Swedish Twin Registry to test the hypothesis that greater positive change in loneliness predicts greater dementia risk. We then used a sample of 1,632 pairs of twins to evaluate the hypothesis that effects of change in loneliness on dementia risk would remain after adjusting for effects of genetic and environmental variance. Phenotypic model results suggest that mild levels of baseline loneliness predict greater dementia risk. Contrary to our hypothesis, change in loneliness did not correlate with dementia risk, regardless of whether genetic and environmental selection confounds were taken into account. Worsening loneliness with age may not confer greater dementia risk.
RESUMEN
Because of limited free diffusion in the cytoplasm, viruses must use active transport mechanisms to move intracellularly. Nevertheless, how the plant single-stranded DNA begomoviruses hijack the host intracytoplasmic transport machinery to move from the nucleus to the plasmodesmata remains enigmatic. Here, we identified nuclear shuttle protein (NSP)-interacting proteins from Arabidopsis (Arabidopsis thaliana) by probing a protein microarray and demonstrated that the cabbage leaf curl virus NSP, a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA, interacts in planta with an endosomal vesicle-localized, plant-specific syntaxin-6 protein, designated NSP-interacting syntaxin domain-containing protein (NISP). NISP displays a proviral function, unlike the syntaxin-6 paralog AT2G18860 that failed to interact with NSP. Consistent with these findings, nisp-1 mutant plants were less susceptible to begomovirus infection, a phenotype reversed by NISP complementation. NISP-overexpressing lines accumulated higher levels of vDNA than wild-type. Furthermore, NISP interacted with an NSP-interacting GTPase (NIG) involved in NSP-vDNA nucleocytoplasmic translocation. The NISP-NIG interaction was enhanced by NSP. We also showed that endosomal NISP associates with vDNA. NISP may function as a docking site for recruiting NIG and NSP into endosomes, providing a mechanism for the intracytoplasmic translocation of the NSP-vDNA complex toward and from the cell periphery.
Asunto(s)
Arabidopsis , Begomovirus , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/virología , Begomovirus/fisiología , Núcleo Celular/metabolismoRESUMEN
BACKGROUND: Family caregivers of people living with dementia benefit from supportive service use to address care needs associated with caregiving. Yet, research consistently demonstrates low rates of service use. Existing research has focused on barriers and facilitators to service use, with few studies examining the influence of caregivers' environmental context which often patterns social advantage and health services accessibility. OBJECTIVE: To describe the perspectives of caregivers residing in socially disadvantaged areas have in regards to utilizing supportive services. METHODS: Ten informal caregivers residing in socially disadvantaged areas participated in in-depth interviews that were analyzed using thematic analysis. RESULTS: Across all interviews, caregivers spontaneously described common precedents of service use (crisis or accumulation of unmet needs) and a distinct sequence of stages (seeking, initiating, and utilizing) surrounding service engagement. Major themes characterizing caregivers' experiences throughout service engagement highlight the varied influence of personal, familial, health, and social system-related factors. Findings demonstrate that caregivers may have different service needs as dementia progresses and that gerontological social work practice can facilitate service use. CONCLUSION: While preliminary, these findings provide important insights into new domains that can be further examined in future research and intervention efforts to improve supportive service use in socially disadvantaged and underserved communities.