General Practitioners' Views And Experiences Of Loneliness In Their Older Adult Patients

Background: Loneliness is associated with numerous detrimental effects on physical health, mental health, cognition, and lifestyle. Older adults are one of the groups at highest risk of loneliness, and indeed about 46% of older adults in England are lonely. Those experiencing loneliness visit their General Practitioner (GP) more frequently than those who are not, which has the capacity to put a strain on GPs and primary care waiting lists and costs. There is some literature on GPs’ experiences of other social problems, but it is yet unknown how GPs in the UK perceive and work with loneliness in older adult patients. Aims: To explore GPs’ views and experiences of loneliness within their older adult patients. Method: A qualitative approach was taken for this research and followed a social constructivist perspective. 19 GPs were recruited using researcher contacts, snowballing, and purposive sampling. Individual semi-structured interviews were conducted either in person or over the telephone. Data were transcribed and analysed using thematic analysis Findings: Five over-arching themes and 14 corresponding sub-themes were presented. GPs’ definitions of loneliness and its prevalence in our society is discussed. GPs held a medicalised and individualistic view regarding loneliness. They discussed their barriers to raising the topic, as well as the social stigma surrounding loneliness for both GP and patient. GPs felt powerless in their ability to fix the problem, and tended to use self-protection strategies. Further need for GP support and system improvements were discussed. Conclusions: Study findings are discussed in the context of relevant theories and literature. Implications include greater emphasis on social problems like loneliness in GP training, more practical and emotional support for qualified GPs, and a clearer more streamlined approach to managing loneliness presentations in primary care. Strengths and limitations of the study are discussed, and avenues for future research suggested

Engaging ‘hard to reach’ groups in health promotion: the views of older people and professionals from a qualitative study in England

Background Older people living in deprived areas, from black and minority ethnic groups (BME) or aged over 85 years (oldest old) are recognised as ‘hard to reach’. Engaging these groups in health promotion is of particular importance when seeking to target those who may benefit the most and to reduce health inequalities. This study aimed to explore what influences them practicing health promotion and elicit the views of cross-sector professionals with experiences of working with ‘hard to reach’ older people, to help inform best practice on engagement. Methods ‘Hard to reach’ older people were recruited through primary care by approaching those not attending for preventative healthcare, and via day centres. Nineteen participated in an interview (n = 15) or focus group (n = 4); including some overlaps: 17 were from a deprived area, 12 from BME groups, and five were oldest old. Cross-sector health promotion professionals across England with experience of health promotion with older people were identified through online searches and snowball sampling. A total of 31 of these 44 professionals completed an online survey including open questions on barriers and facilitators to uptake in these groups. Thematic analysis was used to develop a framework of higher and lower level themes. Interpretations were discussed and agreed within the team. Results Older people’s motivation to stay healthy and independent reflected their everyday behaviour including practicing activities to feel or stay well, level of social engagement, and enthusiasm for and belief in health promotion. All of the oldest old reported trying to live healthily, often facilitated by others, yet sometimes being restricted due to poor health. Most older people from BME groups reported a strong wish to remain independent which was often positively influenced by their social network. Older people living in deprived areas reported reluctance to undertake health promotion activities, conveyed apathy and reported little social interaction. Cross-sector health professionals consistently reported similar themes as the older people, reinforcing the views of the older people through examples. Conclusions The study shows some shared themes across the three ‘hard-to-reach’ groups but also some distinct differences, suggesting that a carefully outlined strategy should be considered to reach successfully the group targeted.Peer reviewedFinal Published versio

Static Wettability of Differently Mechanically Treated and Amphiphobic-Coated Aluminium Surfaces

Wettability, roughness and surface treatment methods are essential for the majority of practical applications, where liquid–solid surface interactions take place. The present study experimentally investigated the influence of different mechanical surface treatment methods on the static wettability of uncoated and amphiphobic-coated aluminium alloy (AlMg3) samples, specially focusing on the interaction between surface finishing and coating. Five different surfaces were prepared: as-received substrate, polished, sandpapered, fleece-abraded and sandblasted. After characterisation, the samples were spray-coated using an amphiphobic coating. The characterisation of the uncoated and coated samples involved measurements of the roughness parameters and the apparent contact angles of demineralized water and rapeseed oil. The coating was initially characterised regarding its adhesion to the sample and elevated temperature stability. The applied surface treatments resulted in the scattered sample roughness in the range of Sa = 0.3–15.8 µm, water contact angles of θap,w = 78°–106° and extremely low oil contact angles. Coating the samples more than doubled the surface roughness to Sa = 13.3–29 µm, whereas the initial surface treatment properties (structure, anisotropy, etc.) were entirely repressed by the coating properties. Coating led the water contact angles to increase to θap,w_coated = 162°–173° and even more pronounced oil contact angles to increase to θap,o_coated = 139°–150°, classifying the surfaces as superhydrophobic and oleophobic

Strategies to improve engagement of 'hard to reach' older people in research on health promotion: : a systematic review

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: This review aimed to identify facilitators, barriers and strategies for engaging 'hard to reach' older people in research on health promotion; the oldest old (≥80 years), older people from black and minority ethnic groups (BME) and older people living in deprived areas. Methods: Eight databases were searched to identify eligible studies using quantitative, qualitative, and mixed research methods. Using elements of narrative synthesis, engagement strategies, and reported facilitators and barriers were identified, tabulated and analysed thematically for each of the three groups of older people. Results: Twenty-three studies (3 with oldest-old, 16 with BME older people, 2 within deprived areas, 1 with both oldest-old and BME, 1 with both BME and deprived areas) were included. Methods included 10 quantitative studies (of which 1 was an RCT), 12 qualitative studies and one mixed-methods study. Facilitators for engaging the oldest old included gaining family support and having flexible sessions. Facilitators for BME groups included building trust through known professionals/community leaders, targeting personal interests, and addressing ethnic and cultural characteristics. Among older people in deprived areas, facilitators for engagement included encouragement by peers and providing refreshments. Across all groups, barriers for engagement were deteriorating health, having other priorities and lack of transport/inaccessibility. Feeling too tired and lacking support from family members were additional barriers for the oldest old. Similarly, feeling too tired and too old to participate in research on health promotion were reported by BME groups. Barriers for BME groups included lack of motivation and self-confidence, and cultural and language differences. Barriers identified in deprived areas included use of written recruitment materials. Strategies to successfully engage with the oldest old included home visits and professionals securing consent if needed. Strategies to engage older people from BME groups included developing community connections and organising social group sessions. Strategies to engage with older people in deprived areas included flexibility in timing and location of interventions. Conclusions: This review identified facilitators, barriers and strategies for engaging 'hard to reach' older people in health promotion but research has been mainly descriptive and there was no high quality evidence on the effectiveness of different approaches.Peer reviewedFinal Published versio

The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of alpha-synuclein, and enhances its secretion and nuclear localization in cells

A novel mutation in the alpha-Synuclein (alpha-Syn) gene "G51D" was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on the aggregation, cellular and biophysical properties of alpha-Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results show that the G51D mutation significantly attenuates alpha-Syn aggregation in vitro. Moreover, it disrupts local helix formation in the presence of SDS, decreases binding to lipid vesicles C-terminal to the site of mutation and severely inhibits helical folding in the presence of acidic vesicles. When expressed in yeast, alpha-Syn(G51D) behaves similarly to alpha-Syn(A30P), as both exhibit impaired membrane association, form few inclusions and are non-toxic. In contrast, enhanced secreted and nuclear levels of the G51D mutant were observed in mammalian cells, as well as in primary neurons, where alpha-Syn(G51D) was enriched in the nuclear compartment, was hyper-phosphorylated at S129 and exacerbated alpha-Syn-induced mitochondrial fragmentation. Finally, post-mortem human brain tissues of alpha-Syn(G51D) cases were examined, and revealed only partial colocalization with nuclear membrane markers, probably due to post-mortem tissue delay and fixation. These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of alpha-Syn aggregation

The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of alpha-synuclein, and enhances its secretion and nuclear localization in cells

A novel mutation in the alpha-Synuclein (alpha-Syn) gene "G51D" was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on the aggregation, cellular and biophysical properties of alpha-Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results show that the G51D mutation significantly attenuates alpha-Syn aggregation in vitro. Moreover, it disrupts local helix formation in the presence of SDS, decreases binding to lipid vesicles C-terminal to the site of mutation and severely inhibits helical folding in the presence of acidic vesicles. When expressed in yeast, alpha-Syn(G51D) behaves similarly to alpha-Syn(A30P), as both exhibit impaired membrane association, form few inclusions and are non-toxic. In contrast, enhanced secreted and nuclear levels of the G51D mutant were observed in mammalian cells, as well as in primary neurons, where alpha-Syn(G51D) was enriched in the nuclear compartment, was hyper-phosphorylated at S129 and exacerbated alpha-Syn-induced mitochondrial fragmentation. Finally, post-mortem human brain tissues of alpha-Syn(G51D) cases were examined, and revealed only partial colocalization with nuclear membrane markers, probably due to post-mortem tissue delay and fixation. These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of alpha-Syn aggregation

Health promotion interventions for community-dwelling older people with mild or pre-frailty : a systematic review and meta-analysis

BACKGROUND: Mild or pre-frailty is common and associated with increased risks of hospitalisation, functional decline, moves to long-term care, and death. Little is known about the effectiveness of health promotion in reducing these risks. This systematic review aimed to synthesise randomised controlled trials (RCTs) evaluating home and community-based health promotion interventions for older people with mild/pre-frailty. METHODS: We searched 20 bibliographic databases and 3 trials registers (January 1990 - May 2016) using mild/pre-frailty and associated terms. We included randomised controlled and crossover trials of health promotion interventions for community-dwelling older people (65+ years) with mild/pre-frailty and excluded studies focussing on populations in hospital, long term care facilities or with a specific condition. Risk of bias was assessed by two reviewers using the Cochrane Risk of Bias tool. We pooled study results using standardised mean differences (SMD) where possible and used narrative synthesis where insufficient outcome data were available. RESULTS: We included 10 articles reporting on seven trials (total n = 506 participants) and included five trials in a meta-analysis. Studies were predominantly small, of limited quality and six studies tested group exercise alone. One study additionally investigated a nutrition and exercise intervention and one evaluated telemonitoring. Interventions of exercise in groups showed mixed effects on functioning (no effects on self-reported functioning SMD 0.19 (95% CI -0.57 to 0.95) n = 3 studies; positive effects on performance-based functioning SMD 0.37 (95% CI 0.07 to 0.68) n = 3 studies). No studies assessed moves to long-term care or hospitalisations. CONCLUSIONS: Currently the evidence base is of insufficient size, quality and breadth to recommend specific health promotion interventions for older people with mild or pre- frailty. High quality studies of rigorously developed interventions are needed

Freezing of gait and fall detection in Parkinson’s disease using wearable sensors:a systematic review

Despite the large number of studies that have investigated the use of wearable sensors to detect gait disturbances such as Freezing of gait (FOG) and falls, there is little consensus regarding appropriate methodologies for how to optimally apply such devices. Here, an overview of the use of wearable systems to assess FOG and falls in Parkinson’s disease (PD) and validation performance is presented. A systematic search in the PubMed and Web of Science databases was performed using a group of concept key words. The final search was performed in January 2017, and articles were selected based upon a set of eligibility criteria. In total, 27 articles were selected. Of those, 23 related to FOG and 4 to falls. FOG studies were performed in either laboratory or home settings, with sample sizes ranging from 1 PD up to 48 PD presenting Hoehn and Yahr stage from 2 to 4. The shin was the most common sensor location and accelerometer was the most frequently used sensor type. Validity measures ranged from 73–100% for sensitivity and 67–100% for specificity. Falls and fall risk studies were all home-based, including samples sizes of 1 PD up to 107 PD, mostly using one sensor containing accelerometers, worn at various body locations. Despite the promising validation initiatives reported in these studies, they were all performed in relatively small sample sizes, and there was a significant variability in outcomes measured and results reported. Given these limitations, the validation of sensor-derived assessments of PD features would benefit from more focused research efforts, increased collaboration among researchers, aligning data collection protocols, and sharing data sets

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Unique Cell-Type-Specific Distributions and Functions of Brain MicroRNAs

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. The first miRNA was discovered less than 20 years ago in the context of studying Caenorabditis elegans development. The discovery of the second miRNA only 10 years ago led to knowledge that these small regulatory RNAs are widely expressed in eukaryotic organisms and involved in almost all cellular processes. It is generally believed that miRNAs predominantly bind to complementary sequences within the 3' untranslated region (3'UTR) of target mRNAs and promote target degradation and/or inhibit target translation. The central nervous system is composed of four principal cell types: neurons, astrocytes, oligodendrocytes and microglia. Although miRNAs are known to regulate development and adult functions of neural cells, a genome-wide profiling of miRNA expression across the four cell types had not previously been performed. We therefore undertook this challenge and globally compared miRNA expression in the four discrete neural cell types and discovered that they differ extensively in their miRNA profiles. The global impact and mechanistic determinants of miRNAs on gene regulation is of high current interest. Recent studies have shown that miRNAs play an important role in tissue-specific protein expression, most notably during early development and cell specification. In particular, several miRNAs have been shown to have important deterministic roles in neuronal or glial fate development. We expanded the known repertoire of miRNAs functioning in neural cell fate specification by showing that neuron-specific miR-376a and miR-434 promote neuronal differentiation, while glia-specific miR-223, miR-146a, miR-19 and miR-32 inhibit neuronal differentiation. Previous genomic analyses inferred that miRNAs have had a significant impact on the 3'UTR evolution, and noted that mammalian miRNAs typically have expression levels reciprocal to those of their targets. Consistent with the latter, a recent genome-wide study concluded that mammalian miRNAs predominantly lead to degradation of their target mRNAs. However, conflicting views existed as to the relevance of these findings in neural cells, possibly due to the previous lack of cellular resolution of miRNA expression. We addressed this issue on a genome-wide scale by comparing cell-type-specific mRNA and miRNA expression in isolated primary cultures. These analyses showed that, similar to the previously described findings for non-neural tissues and cell types, glial cells show prominent reciprocity of miRNA and predicted target expression and demonstrate functional effects consistent with preventing inappropriate expression of neuron-specific proteins. In contrast, neuron-specific miRNAs surprisingly showed a correlation to the expression of their targets. We further demonstrated that two of these neuron-specific miRNAs, miR-135b and miR-137, regulate the expression of mRNAs encoding important synaptic proteins and that the dynamics of these mRNA-miRNA pairs are regulated in a neural activity-dependent manner. The unexpected finding that neuronal miRNAs have an exceptional positively correlated relationship to their targets adds a new layer of complexity to the current understanding post-transcriptional gene expression regulation by miRNAs. Moreover, additional features of the unique relationships of miRNAs and signaling in neuronal cells suggest how miRNAs may help neurons regulate their highly specialized functions. MiRNAs have also been implicated as modulators of the pathogenesis of neurodegenerative disorders. Interestingly, since one miRNA can regulate the expression of tens or hundreds of genes, manipulating miRNA levels can have broad positive or negative effects on the disease development and progression. We observed that miRNA-22 regulates expression of multiple neurodegeneration-related genes and that enhancing expression of miRNA-22 in models of neurodegeneration has a significant neuroprotective effect. We therefore propose miRNA-22 as a new candidate therapeutic capable of preventing neurodegeneration, which may be of benefit in a number of human afflictions for which there is currently a high unmet medical need