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1.
Cochrane Database Syst Rev ; 3: CD013059, 2024 03 19.
Article in English | MEDLINE | ID: mdl-38501686

ABSTRACT

BACKGROUND: Depression is common amongst older people residing in long-term care (LTC) facilities. Currently, most residents treated for depression are prescribed antidepressant medications, despite the potential availability of psychological therapies that are suitable for older people and a preference amongst many older people for non-pharmacological treatment approaches. OBJECTIVES: To assess the effect of psychological therapies for depression in older people living in LTC settings, in comparison with treatment as usual, waiting list control, and non-specific attentional control; and to compare the effectiveness of different types of psychological therapies in this setting. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, five other databases, five grey literature sources, and two trial registers. We performed reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was 31 October 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and cluster-RCTs of any type of psychological therapy for the treatment of depression in adults aged 65 years and over residing in a LTC facility. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles/abstracts and full-text manuscripts for inclusion. Two review authors independently performed data extraction and risk of bias assessments using the Cochrane RoB 1 tool. We contacted study authors for additional information where required. Primary outcomes were level of depressive symptomatology and treatment non-acceptability; secondary outcomes included depression remission, quality of life or psychological well-being, and level of anxious symptomatology. We used Review Manager 5 to conduct meta-analyses, using pairwise random-effects models. For continuous data, we calculated standardized mean differences and 95% confidence intervals (CIs), using endpoint data, and for dichotomous data, we used odds ratios and 95% CIs. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 19 RCTs with 873 participants; 16 parallel group RCTs and three cluster-RCTs. Most studies compared psychological therapy (typically including elements of cognitive behavioural therapy, behavioural therapy, reminiscence therapy, or a combination of these) to treatment as usual or to a condition controlling for the effects of attention. We found very low-certainty evidence that psychological therapies were more effective than non-therapy control conditions in reducing symptoms of depression, with a large effect size at end-of-intervention (SMD -1.04, 95% CI -1.49 to -0.58; 18 RCTs, 644 participants) and at short-term (up to three months) follow-up (SMD -1.03, 95% CI -1.49 to -0.56; 16 RCTs, 512 participants). In addition, very low-certainty evidence from a single study with 82 participants indicated that psychological therapy was associated with a greater reduction in the number of participants presenting with major depressive disorder compared to treatment as usual control, at end-of-intervention and short-term follow-up. However, given the limited data on the effect of psychological therapies on remission of major depressive disorder, caution is advised in interpreting this result. Participants receiving psychological therapy were more likely to drop out of the trial than participants receiving a non-therapy control (odds ratio 3.44, 95% CI 1.19 to 9.93), which may indicate higher treatment non-acceptability. However, analyses were restricted due to limited dropout case data and imprecise reporting, and the finding should be interpreted with caution. There was very low-certainty evidence that psychological therapy was more effective than non-therapy control conditions in improving quality of life and psychological well-being at short-term follow-up, with a medium effect size (SMD 0.51, 95% CI 0.19 to 0.82; 5 RCTs, 170 participants), but the effect size was small at postintervention (SMD 0.40, 95% CI -0.02 to 0.82; 6 RCTs, 195 participants). There was very low-certainty evidence of no effect of psychological therapy on anxiety symptoms postintervention (SMD -0.68, 95% CI -2.50 to 1.14; 2 RCTs, 115 participants), although results lacked precision, and there was insufficient data to determine short-term outcomes. AUTHORS' CONCLUSIONS: This systematic review suggests that cognitive behavioural therapy, behavioural therapy, and reminiscence therapy may reduce depressive symptoms compared with usual care for LTC residents, but the evidence is very uncertain. Psychological therapies may also improve quality of life and psychological well-being amongst depressed LTC residents in the short term, but may have no effect on symptoms of anxiety in depressed LTC residents, compared to control conditions. However, the evidence for these effects is very uncertain, limiting our confidence in the findings. The evidence could be strengthened by better reporting and higher-quality RCTs of psychological therapies in LTC, including trials with larger samples, reporting results separately for those with and without cognitive impairment and dementia, and longer-term outcomes to determine when effects wane.


Subject(s)
Cognitive Behavioral Therapy , Depression , Humans , Aged , Depression/therapy , Long-Term Care , Psychotherapy/methods , Behavior Therapy/methods , Quality of Life
2.
Contact (Thousand Oaks) ; 7: 25152564241232196, 2024.
Article in English | MEDLINE | ID: mdl-38405037

ABSTRACT

The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans-Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis.

3.
Contact (Thousand Oaks) ; 7: 25152564241229272, 2024.
Article in English | MEDLINE | ID: mdl-38327560

ABSTRACT

Oxysterol-binding protein (OSBP)-related proteins (ORPs) 5 and 8 have been shown to deplete the lipid phosphatidylinositol 4-phosphate (PI4P) at sites of membrane contact between the endoplasmic reticulum (ER) and plasma membrane (PM). This is believed to be caused by transport of PI4P from the PM to the ER, where PI4P is degraded by an ER-localized SAC1 phosphatase. This is proposed to power the anti-port of phosphatidylserine (PS) lipids from ER to PM, up their concentration gradient. Alternatively, ORPs have been proposed to sequester PI4P, dependent on the concentration of their alternative lipid ligand. Here, we aimed to distinguish these possibilities in living cells by orthogonal targeting of PI4P transfer and degradation to PM-mitochondria contact sites. Surprisingly, we found that orthogonal targeting of SAC1 to mitochondria enhanced PM PI4P turnover independent of targeting to contact sites with the PM. This turnover could be slowed by knock-down of soluble ORP2, which also has a major impact on PM PI4P levels even without SAC1 over-expression. The data reveal a role for contact site-independent modulation of PM PI4P levels and lipid antiport.

4.
bioRxiv ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38187665

ABSTRACT

The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis.

5.
bioRxiv ; 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-37693626

ABSTRACT

Oxysterol binding protein (OSBP)-related proteins (ORPs) 5 and 8 have been shown to deplete the lipid phosphatidylinositol 4-phosphate (PI4P) at sites of membrane contact between the endoplasmic reticulum (ER) and plasma membrane (PM). This is believed to be caused by transport of PI4P from the PM to the ER, where PI4P is degraded by an ER-localized SAC1 phosphatase. This is proposed to power the anti-port of phosphatidylserine (PS) lipids from ER to PM, up their concentration gradient. Alternatively, ORPs have been proposed to sequester PI4P, dependent on the concentration of their alternative lipid ligand. Here, we aimed to distinguish these possibilities in living cells by orthogonal targeting of PI4P transfer and degradation to PM-mitochondria contact sites. Surprisingly, we found that orthogonal targeting of SAC1 to mitochondria enhanced PM PI4P turnover independent of targeting to contact sites with the PM. This turnover could be slowed by knock-down of soluble ORP2, which also has a major impact on PM PI4P levels even without SAC1 over-expression. The data reveal a role for contact site-independent modulation of PM PI4P levels and lipid antiport.

6.
Forensic Sci Int Genet ; 67: 102935, 2023 11.
Article in English | MEDLINE | ID: mdl-37797418

ABSTRACT

Demand for bear bile, a prized component of traditional Asian medicines, threaten Asiatic and sun bear population sustainability. While laws exist to prevent poaching and trafficking of bear parts and derivatives, smuggling persists with demand extending to surrogate species, including American black bears (Ursus americanus). Mitochondrial DNA (mtDNA) sequencing can identify products putatively containing biological bear material but can be undermined by PCR inhibitors in bile and a lack of sensitivity at trace levels. Quantitative PCR (qPCR) assays can be used to distinguish between closely related target species, while concomitantly evaluating inhibition and false negative results in low quality/quantity DNA applications. Herein, we develop a multiplexed qPCR assay to detect and differentiate among bear species, including highly diluted bile samples mixed within liquors as common dilutants. The assay detects as little as 10 locus copies/reaction of bear DNA with 95% confidence, distinguishing among sun, Asiatic and American black bears. Demonstrating the sensitivity and applicability of this assay in context of current bile mixture recipes, dilutions of 1:5,000 bile with ethanol, red wine, and spirits, all yielded clear quantifiable detections, where our data suggests as little as 1 drop of bile per 750 mL bottle of alcohol would still exceed the limits of detection (e.g., 1:15000 dilution or <0.05 mL bile per 750 mL bottle). Overall, this study provides a rapid, sensitive, and specific test to identify and distinguish among bear species commonly used for bile production to aid wildlife enforcement applications.


Subject(s)
Bile , Ursidae , Humans , Animals , Animals, Wild/genetics , Ursidae/genetics , Polymerase Chain Reaction , DNA, Mitochondrial/genetics
7.
J Cell Sci ; 136(16)2023 08 15.
Article in English | MEDLINE | ID: mdl-37534432

ABSTRACT

The lipid molecule phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] controls all aspects of plasma membrane (PM) function in animal cells, from its selective permeability to the attachment of the cytoskeleton. Although disruption of PI(4,5)P2 is associated with a wide range of diseases, it remains unclear how cells sense and maintain PI(4,5)P2 levels to support various cell functions. Here, we show that the PIP4K family of enzymes, which synthesize PI(4,5)P2 via a minor pathway, also function as sensors of tonic PI(4,5)P2 levels. PIP4Ks are recruited to the PM by elevated PI(4,5)P2 levels, where they inhibit the major PI(4,5)P2-synthesizing PIP5Ks. Perturbation of this simple homeostatic mechanism reveals differential sensitivity of PI(4,5)P2-dependent signaling to elevated PI(4,5)P2 levels. These findings reveal that a subset of PI(4,5)P2-driven functions might drive disease associated with disrupted PI(4,5)P2 homeostasis.


Subject(s)
Phosphatidylinositol 4,5-Diphosphate , Signal Transduction , Animals , Phosphatidylinositol 4,5-Diphosphate/metabolism , Signal Transduction/physiology , Cell Membrane/metabolism , Phosphatidylinositols/metabolism , Homeostasis
8.
Gen Hosp Psychiatry ; 84: 149-157, 2023.
Article in English | MEDLINE | ID: mdl-37490825

ABSTRACT

OBJECTIVE: We report on women's mental health care desires following a miscarriage, medical termination, or abortion. METHOD: 689 women completed a questionnaire on reproductive history, health care following miscarriage/medical termination/abortion, and current mental health. Descriptive statistics and logistic regression analyses examined: miscarriage/termination/abortion incidence, desires for mental health support following miscarriages/terminations/abortions, and current mental health. RESULTS: Of 365 women with a pregnancy history, 37% reported ≥1 miscarriage, 9% ≥1 medical termination, 16% ≥1 abortion, and 3% endorsed all three. Current mental health did not differ between women with a history of miscarriage/termination/abortion and those with only live births (p = 0.82). Following miscarriage, 68% of women discussed options for the medical management of pregnancy loss with their provider, 32% discussed grief/loss, and 25% received mental health care recommendations. Engagement in mental health services was reported by 16% of women with a history of miscarriage, 38% after medical termination, and 19% following an abortion. Of women who became pregnant after their most recent miscarriage/termination/abortion and did not receive mental health care, 55% wished they had received services during the subsequent pregnancy. CONCLUSIONS: Women desire mental health care after miscarriages, medical terminations, or abortions, warranting improved access to mental health care for these individuals.


Subject(s)
Abortion, Induced , Abortion, Spontaneous , Mental Health Services , Pregnancy , Female , Humans , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/therapy , Abortion, Spontaneous/psychology , Mental Health , Abortion, Induced/psychology , Surveys and Questionnaires
9.
Aging Ment Health ; 27(2): 243-250, 2023 02.
Article in English | MEDLINE | ID: mdl-35100918

ABSTRACT

OBJECTIVES: To investigate electronic care notes to better understand reporting and management of neuropsychiatric symptoms (NPS) by residential aged care (RAC) staff. METHODS: We examined semi-structured care notes from electronic healthcare notes of 77 residents (67% female; aged 67-101; 79% with formal dementia diagnosis) across three RAC facilities. As part of standard clinical practice, staff documented the NPS presentation and subsequent management amongst residents. Using a mixed-method approach, we analyzed the type of NPS reported and explored care staff responses to NPS using inductive thematic analysis. RESULTS: 465 electronic care notes were recorded during the 18-month period. Agitation-related behaviors were most frequently reported across residents (48.1%), while psychosis (15.6%), affective symptoms (14.3%), and apathy (1.3%) were less often reported. Only 27.5% of the notes contained information on potential causes underlying NPS. When faced with NPS, care staff responded by either providing emotional support, meeting resident's needs, removing identified triggers, or distracting. CONCLUSION: Results suggest that RAC staff primarily detected and responded to those NPS they perceived as distressing. Findings highlight a potential under-recognition of specific NPS types, and lack of routine examination of NPS causes or systematic assessment and management of NPS. These observations are needed to inform the development and implementation of non-pharmacological interventions and care programs targeting NPS in RAC.Supplemental data for this article is available online at https://doi.org/10.1080/13607863.2022.2032597 .


Subject(s)
Dementia , Psychotic Disorders , Aged , Humans , Female , Male , Nursing Homes , Dementia/diagnosis , Dementia/therapy , Dementia/psychology , Homes for the Aged , Delivery of Health Care
10.
Clin Gerontol ; 46(4): 498-510, 2023.
Article in English | MEDLINE | ID: mdl-36163627

ABSTRACT

OBJECTIVES: Depression and cognitive impairment are disabling conditions that commonly occur together in older adults. The interaction is challenging when choosing appropriate measurement scales. This review aimed to summarize the scales to measure depression symptoms in older people with cognitive impairment, investigating how cognitive impairment is related to the choice of measurement, and how the setting may affect the choice of measurement. METHODS: A scoping review of literature published between 2015 and 2021. RESULTS: After screening 1580 articles, 26 were included in the review with 11 different measures of depression symptoms identified. The measures mostly commonly used were the Geriatric Depression Scale (GDS), Cornell Scale for Depression in Dementia (CSDD) and the Neuropsychiatric Inventory (NPI-Q). Most studies did not report on the usability of depression scales used with people with cognitive impairment and only two scales (CSDD and NPI-Q, not GDS) have been validated for use with this population. CONCLUSIONS: Severe cognitive impairment was under-represented in the identified studies, and no association was detected between study setting, cognitive impairment and type of measure used. CLINICAL IMPLICATIONS: Clinicians and researchers should consider both the cognitive status of participants and the setting they live in when choosing a measure of depression symptoms.


Subject(s)
Cognitive Dysfunction , Dementia , Humans , Aged , Depression/complications , Depression/diagnosis , Depression/epidemiology , Dementia/psychology , Psychiatric Status Rating Scales , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis
11.
Nutrients ; 14(13)2022 Jun 29.
Article in English | MEDLINE | ID: mdl-35807902

ABSTRACT

Despite growing awareness of the financial burden that a cancer diagnosis places on a household, there is limited understanding of the risk for food insecurity among this population. The current study reviewed literature focusing on the relationship between food insecurity, cancer, and related factors among cancer survivors and their caregivers. In total, 49 articles (across 45 studies) were reviewed and spanned topic areas: patient navigation/social worker role, caregiver role, psychosocial impacts, and food insecurity/financial toxicity. Patient navigation yielded positive impacts including perceptions of better quality of care and improved health related quality of life. Caregivers served multiple roles: managing medications, emotional support, and medical advocacy. Subsequently, caregivers experience financial burden with loss of employment and work productivity. Negative psychosocial impacts experienced by cancer survivors included: cognitive impairment, financial constraints, and lack of coping skills. Financial strain experienced by cancer survivors was reported to influence ratings of physical/mental health and symptom burden. These results highlight that fields of food insecurity, obesity, and cancer control have typically grappled with these issues in isolation and have not robustly studied these factors in conjunction. There is an urgent need for well-designed studies with appropriate methods to establish key determinants of food insecurity among cancer survivors with multidisciplinary collaborators.


Subject(s)
Cancer Survivors , Neoplasms , Adaptation, Psychological , Caregivers/psychology , Food Insecurity , Food Supply , Humans , Quality of Life/psychology
12.
Dementia (London) ; 21(3): 899-917, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35135380

ABSTRACT

Undertaking co-design with the end users of services has rapidly evolved as the best-practice approach to program design, development and implementation. Increased interest in using participatory co-design in dementia care has drawn attention to the need for evidence-informed methods for facilitating the meaningful involvement of people with dementia and their family carers in co-design activities. The aim of this paper is to describe the co-design framework used in the co-design of a dementia specialist training program for home care workers. The Promoting Independence Through quality dementia Care at Home program is a successful example of co-design methodology used across multiple project stages and with various stakeholder groups, including people living with dementia, family carers, home care workers, managers and researchers. Co-design methods were tailored to each stage, purpose, and stakeholder group, and to facilitate the involvement of people living with dementia. Findings provide unique insights into optimising input from co-design partners, including people living with dementia; the methodology, conditions and requirements for participants to co-design and implement ideas; and perspectives on the enablers and challenges of using co-design in this population. In this paper, we present a comprehensive approach for involving people living with dementia as active and equal contributors in inclusive and meaningful participatory co-design.


Subject(s)
Dementia , Home Care Services , Home Health Aides , Caregivers , Dementia/therapy , Humans , Quality of Health Care
13.
Pilot Feasibility Stud ; 8(1): 41, 2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35172894

ABSTRACT

BACKGROUND: With increasing numbers of people living with dementia relying on family to care for them at home, there is an urgent need for practical and evidence-based programs to support carers in maintaining their mental health and well-being. The objective of this study was to evaluate the acceptability and feasibility of a modified STrAtegies for RelaTives (START) program delivered online (START-online). METHOD: A mixed-methods non-blinded evaluation of START-online (using Zoom as videoconferencing platform) for acceptability and feasibility (completion rates and qualitative feedback through surveys and focus groups) and quantitative evaluation. This occurred at the National Ageing Research Institute, in metropolitan Victoria, Australia. RESULTS: Twenty-nine eligible carers were referred, 20 (70%) consented to the study. Of these, 16 (80%) completed all 8 sessions, 2 completed only 3 sessions, and 2 withdrew. Carers' qualitative feedback indicated that the therapist interaction was valued, content and online delivery of the program was acceptable. Feedback was mixed on the appropriate stage of caring. CONCLUSION: START-online was feasible and acceptable for carers, including those living outside of metropolitan areas who might otherwise be unable to access face-to-face programs. With the recent COVID-19 pandemic necessitating social distancing to avoid infection, interventions such as this one have increasing relevance in the provision of flexible services.

14.
BMC Geriatr ; 22(1): 42, 2022 01 11.
Article in English | MEDLINE | ID: mdl-35016640

ABSTRACT

BACKGROUND: Our objective was to explore what people receiving and providing care consider to be 'good' in-home care for people living with dementia. METHODS: We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke's six-step approach. RESULTS: Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers' understanding of dementia and its impact; 2) Home care workers' demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers' knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. CONCLUSIONS: It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. TRIAL REGISTRATION: ACTRN 12619000251123 .


Subject(s)
Dementia , Home Care Services , Home Health Aides , Caregivers , Dementia/diagnosis , Dementia/therapy , Focus Groups , Humans
15.
Clin Gerontol ; 45(1): 58-70, 2022.
Article in English | MEDLINE | ID: mdl-34634217

ABSTRACT

OBJECTIVES: This study is the first to obtain data on the prevalence of, contributors to, and supports required for, pandemic-related distress within the residential aged care sector in Australia. A nested mixed-methods approach was used to examine aged care leaders' opinions about the impact of COVID-19 on the mental health of aged care residents and staff. METHODS: A total of 288 senior staff of Australian residential aged care facilities (care managers, clinical care coordinators, and lifestyle team leaders; mean age = 52.7 years, SD = 10.3) completed an online survey between 10th September and 31st October 2020. RESULTS: On average, nearly half of their residents experienced loneliness (41%) and a third experienced anxiety in response to COVID-19 (33%). The most frequently noted contributors to poor mental health among residents were restrictions to recreational outings and watching news coverage relating to COVID-19. Participants emphasized the need for increased access to counseling services and improved mental health training amongst staff. Residential care staff were similarly impacted by the pandemic. More than a third of staff were reported as anxious (36%) and 20% depressed, in response to COVID-19. Staff were worried about introducing COVID-19 into their facility and were impacted by news coverage of COVID-19. Staff would feel supported by financial assistance and by increased staff-resident ratios. CONCLUSIONS: Senior staff perceive that the mental health of Australian aged care residents and staff was negatively impacted by the COVID-19 pandemic. The most noted contributors were identified, as was the mental health support for aged care communities. CLINICAL IMPLICATIONS: This study provides government and policymakers with clear intervention targets for supporting the sector. Clinicians can support residential aged care communities by providing on-site or telehealth counseling, and upskill and train residential aged care staff on how to respond to the emotional needs of residents in response to COVID-19.


Subject(s)
COVID-19 , Aged , Australia , Humans , Mental Health , Pandemics , SARS-CoV-2
16.
J Mol Biol ; 434(2): 167398, 2022 01 30.
Article in English | MEDLINE | ID: mdl-34902431

ABSTRACT

Structural heterogeneity often constrains the characterization of aggregating proteins to indirect or low-resolution methods, obscuring mechanistic details of association. Here, we report progress in understanding the aggregation of Adnectins, engineered binding proteins with an immunoglobulin-like fold. We rationally design Adnectin solubility and measure amide hydrogen/deuterium exchange (HDX) under conditions that permit transient protein self-association. Protein-protein binding commonly slows rates of HDX; in contrast, we find that Adnectin association may induce faster HDX for certain amides, particularly in the C-terminal ß-strand. In aggregation-prone proteins, we identify a pattern of very different rates of amide HDX for residues linked by reciprocal hydrogen bonds in the native structure. These results may be explained by local loss of native structure and formation of an inter-protein interface. Amide HDX induced by self-association, detected here by deliberate modulation of propensity for such interactions, may be a general phenomenon with the potential to expose mechanisms of aggregation by diverse proteins.


Subject(s)
Amides/chemistry , Deuterium/chemistry , Hydrogen/chemistry , Protein Binding , Amino Acid Sequence , Hydrogen Bonding , Models, Molecular , Proteins/chemistry , Solubility
17.
Trials ; 22(1): 949, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34930422

ABSTRACT

BACKGROUND: Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. METHODS: This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs' sense of competence in dementia care provision. DISCUSSION: Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. TRIAL REGISTRATION: anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.


Subject(s)
Dementia , Home Care Services , Caregivers , Dementia/diagnosis , Dementia/therapy , Educational Status , Humans , Quality of Health Care , Randomized Controlled Trials as Topic
18.
BMC Geriatr ; 21(1): 305, 2021 05 12.
Article in English | MEDLINE | ID: mdl-33980168

ABSTRACT

BACKGROUND: This protocol describes an ongoing study of the impact of befriending on depression, anxiety and loneliness in older people living in residential aged care facilities in Australia. While systematic reviews of befriending have indicated positive benefits of befriending for people in a range of ages and settings, there have been no randomised controlled trials (RCTs) of befriending for older people living in residential aged care with depression and no studies of the cost effectiveness of befriending in residential aged care facilities (RACFs) in Australia. METHODS AND ANALYSIS: We are conducting a single blind pragmatic RCT comparing two groups of older people living in RACFs, one receiving an intervention consisting of weekly befriending for 4 months from a trained volunteer and the other receiving treatment as usual. Participants undergo eligibility screening for depression (GDS-15 ≥ 4) and cognitive impairment (GPCog ≥ 4) and assessments at three measurement time points: baseline prior to randomisation, 2 months post-baseline and 4 months post-baseline. The primary outcome measure is depression, and secondary outcome measures are anxiety, loneliness, social isolation and quality of life. The economic evaluation will take the form of a cost-utility analysis based on the outcome of quality of life. The primary and secondary outcomes will be analysed using negative binomial and logistic regressions utilizing the Generalised Estimating Equations approach. DISCUSSION: To our knowledge, this is the first RCT evaluating the effectiveness of befriending on older people with depression living in residential aged care. It is expected that the befriending intervention will reduce the severity of depression symptoms experienced by older people living in residential aged care. If the intervention proves effective it may be incorporated into volunteer training programs and adopted as a way of supporting older people's mental health. TRIAL REGISTRATION: Trial registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR) Number: ACTRN12619000676112 , registered 06/05/2019 - retrospectively registered.


Subject(s)
Depression , Social Support , Aged , Anxiety/diagnosis , Anxiety/epidemiology , Anxiety/therapy , Australia/epidemiology , Depression/diagnosis , Depression/epidemiology , Depression/therapy , Humans , Quality of Life , Treatment Outcome
19.
Psychol Aging ; 36(4): 491-503, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33539147

ABSTRACT

Prospective memory (PM) is a critical determinant of whether a person is able to lead an independent life. Because PM declines in late adulthood, an important question is therefore whether, and if so, which types, of PM interventions might lead to meaningful benefits. In the present study, we randomly assigned older adults to one of four conditions, in three of which participants received a structured PM intervention (Restorative, Compensatory, and Combined Restorative and Compensatory); the fourth was an Active Control condition. The results showed that there were significant gains on the PM training task used for both the Restorative and Combined conditions. We then analyzed change in PM tasks that were independent of the PM training task (Near Transfer). Only the Combined condition led to post-training improvement. Finally, we analyzed performance on measures of untrained cognitive abilities and everyday functioning: Far transfer effects were not evident for any intervention. These data align with prior literature in showing that interventions that target a single cognitive ability do not reliably generate far transfer effects, and additionally extend our understanding of these effects in two important ways. Firstly, they indicate that, even when the memory challenges that older adults are most concerned about are the direct target of restorative training, transfer effects to untrained cognitive domains may be difficult to achieve. Secondly, they indicate that for older adults whose primary goal is to enhance PM function, combining Restorative and Compensatory approaches is an effective approach. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Cognition/physiology , Learning/physiology , Aged , Aged, 80 and over , Aging , Female , Humans , Male , Middle Aged
20.
Biol Psychiatry ; 89(7): 672-680, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33518264

ABSTRACT

Anxiety disorders are the most prevalent psychiatric disorders in youth and are associated with profound individual impairment and public health costs. Research shows that clinically significant anxiety symptoms manifest in preschool-aged children, and correlates of anxiety symptoms are observable in infancy. Yet, predicting who is at risk for developing anxiety remains an enduring challenge. Predictive biomarkers of anxiety are needed before school age when anxiety symptoms typically consolidate into diagnostic profiles. Increasing evidence indicates that early neural measures implicated in anxiety and anxious temperament may be incorporated with traditional measures of behavioral risk (i.e., behavioral inhibition) to provide more robust classification of pediatric anxiety problems. This review examines the phenomenology of anxiety disorders in early life, highlighting developmental research that interrogates the putative neurocircuitry of pediatric anxiety. First, we discuss enduring challenges in identifying and predicting risk for pediatric anxiety. Second, we summarize emerging evidence for putative neural antecedents and networks underlying risk for pediatric anxiety in the fetal, neonatal, and infant periods that represent novel potential avenues for risk identification and prediction. We focus on evidence examining the importance of early amygdala and extended amygdala circuitry development to the emergence of anxiety. Finally, we discuss the utility of integrating developmental psychopathology and neuroscience to facilitate future research and clinical work.


Subject(s)
Anxiety Disorders , Anxiety , Adolescent , Amygdala , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Neural Networks, Computer , Temperament
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