Lay perceptions of diabetes mellitus and prevention costs and benefits among adults undiagnosed with the condition in Singapore: a qualitative study.

BACKGROUND: Therapeutic lifestyle changes can reduce individual risk of type 2 diabetes (T2D) by up to 58%. In Singapore, rates of preventive practices were low, despite a high level of knowledge and awareness of T2D risk and prevention. The study explored the context of the discrepancy between knowledge and practices in T2D prevention among adults undiagnosed with the condition. METHODS: In-depth interviews with 41 adults explored lay beliefs of T2D and the sources of these perceptions, subjective interpretation of how T2D may impact lives, and perceived costs and benefits of practising preventative behaviours. Purposive sampling was used to maximise the variability of participants in demographic characteristics. Thematic analysis was conducted to identify themes related to the domains of inquiry. RESULTS: Participants' risk perceptions were influenced by familial, social, and cultural contexts of the representation and management of T2D conditions. The adverse effects of T2D were often narrated in food culture. The cost of adopting a healthy diet was perceived at a high cost of life pleasure derived from food consumption and social interactions. Inconveniences, loss of social functions, dependency and distress were the themes related to T2D management. Participants' motivation to preventive practices, such as exercise and weight loss, were influenced by short-term observable benefits. CONCLUSIONS: T2D risk communication needs to be addressed in emotionally impactful and interpersonally salient ways to increase the urgency to adopt preventative behaviours. Shifting perceived benefits from long-term disease prevention to short-term observable wellbeing could reduce the response cost of healthy eating.

A qualitative study of daily activities that inform a process-based model of well-being among Singaporean adults.

BACKGROUND: Individual appraisals of personal well-being consider a spectrum of constructs including the reflections on the degree to which one's life is ultimately secure, meaningful, or valued in the context of dynamic changes in their bio-psycho-social environments. Standardized questionnaires for well-being evaluate an ideal state of health which is operationally defined by abstract constructs. Patient reports describe well-being as a more dynamic construct that relates to how they adapt to successive changes in their life situations. While response shift theory addresses this dynamic nature, little is known about how personal well-being is pursued as personal aspirations evolve. In this study, we identify regularly practiced goal-directed activities reported to contribute to the pursuit of personal well-being. We then propose a taxonomy of these reported activities to inform a process-based model for well-being. METHODS: Purposive sampling was conducted with individuals, 30 to 60 years of age, with diverse ethnicities reflecting the Singaporean population. Individual semi-structured interviews were administered with the primary question: "What are the things or activities you have done in the last two weeks that made you feel like you had a good day?" Probes explored the personally salient meaning of each activity. A thematic approach was used for data analysis followed by a framework analysis to categorize the activities into major themes. RESULTS: We interviewed 40 individuals comprised of 60% female participants. Thematic analysis identified eight types of goal-directed activities, which were categorized under three major themes: (i) Self-Affirming Care through individual self-care and maintaining interpersonal relationships, (ii) Achievement-Focused Tasks as indicated by work-related accomplishments and developing a skill or hobby, (iii) Affiliative Growth and Support as reflected through religious practices and community services. Planned physical activity contributed to self-affirming care and achievement-focused tasks. Social affirming roles were associated with both achievement-focused tasks and affiliative growth and support. CONCLUSIONS: In the dimensions of goal-directed activities identified, there is close alignment between Self-Affirming Care and attachment theory; Achievement-Focused Tasks and self-determination theory; and Affiliative Growth and Support and social mattering. These findings can contribute to a comprehensive process-based model of well-being which is more closely aligned to patient-report appraisals of personal well-being.

Memantine Mitigates Oligodendrocyte Damage after Repetitive Mild Traumatic Brain Injury.

Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment, white matter injury and increased risk of neurodegeneration. Targeted therapies for rmTBI are lacking, though evidence from other injury models indicates that targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic toxicity might mitigate rmTBI-induced injury. We have previously shown that the NMDAR antagonist memantine lessens axonal injury and restores long term potentiation after rmTBI. Here, we evaluated whether the protective effects of memantine include oligodendrocyte specific mechanisms, as prior studies suggest that oligodendrocytes are particularly vulnerable to glutamatergic toxicity. Mice were subjected to rmTBI injury (5 injuries in 5 days) and randomized to treatment with memantine or with vehicle (n = 32/group). At the molecular level, oligodendrocyte counts and function (myelin basic protein, MBP) were assessed by immunohistochemistry and western blot at days 3, 7 and 28 days after the last injury. Axon integrity was assessed by neurofilament light chain (NF-l) expression and axonal ultrastructure was evaluated by electron microscopy. Compared to vehicle-treated mice, memantine-treated mice were protected against oligodendrocyte loss and decreased MBP expression at subacute time points after injury. Memantine treatment also protected against axon damage assessed by NF-l expression. These data suggest that the therapeutic effects of post-concussive NMDAR antagonism may in part work through oligodendrocyte specific mechanisms, which may have implications for long term neurodegenerative sequelae after multiple concussions.

Memantine improves outcomes after repetitive traumatic brain injury.

Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment. Targeted therapies for rmTBI are lacking, though evidence from other injury models indicates that targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic toxicity might mitigate rmTBI-induced neurologic deficits. However, there is a paucity of preclinical or clinical data regarding NMDAR antagonist efficacy in the rmTBI setting. To test whether NMDAR antagonist therapy improves outcomes after rmTBI, mice were subjected to rmTBI injury (4 injuries in 4days) and randomized to treatment with the NMDA antagonist memantine or with vehicle. Functional outcomes were assessed by motor, anxiety/impulsivity and mnemonic behavioral tests. At the synaptic level, NMDAR-dependent long-term potentiation (LTP) was assessed in isolated neocortical slices. At the molecular level, the magnitude of gliosis and tau hyper-phosphorylation was tested by Western blot and immunostaining, and NMDAR subunit expression was evaluated by Western blot and polymerase chain reaction (PCR). Compared to vehicle-treated mice, memantine-treated mice had reduced tau phosphorylation at acute time points after injury, and less glial activation and LTP deficit 1 month after injury. Treatment with memantine also corresponded to normal NMDAR expression after rmTBI. No corresponding protection in behavior outcomes was observed. Here we found NMDAR antagonist therapy may improve histopathological and functional outcomes after rmTBI, though without consistent corresponding improvement in behavioral outcomes. These data raise prospects for therapeutic post-concussive NMDAR antagonism, particularly in athletes and warriors, who suffer functional impairment and neurodegenerative sequelae after multiple concussions.

Environmental Enrichment Mitigates Deficits after Repetitive Mild Traumatic Brain Injury.

Although environmental enrichment has been shown to improve functional and histologic outcomes in pre-clinical moderate-to-severe traumatic brain injury (TBI), there are a paucity of pre-clinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes and those in the military who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance. Here, we evaluated enrichment strategies in an established pre-clinical rmTBI model. Seventy-one male C57BL/6 mice were randomized to two different housing conditions, environmental enrichment (EE) or normal condition (NC), then subjected to rmTBI injury (seven injuries in 9 days) or sham injury (anesthesia only). Functional outcomes in all four groups (NC-TBI, EE-TBI, NC-sham, and EE-sham) were assessed by motor, exploratory/anxiety, and mnemonic behavioral tests. At the synaptic level, N-methyl d-aspartate receptor (NMDAR) subunit expression of phosphorylated glutamate receptor 1 (GluR1), phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII), and calpain were evaluated by western blot. Compared to injured NC-TBI mice, EE-TBI mice had improved memory and decreased anxiety and exploratory activity post-injury. Treatment with enrichment also corresponded to normal NMDAR subunit expression, decreased GluR1 phosphorylation, decreased phosphorylated CaMKII, and normal calpain expression post-rmTBI. These data suggest that enrichment strategies may improve functional outcomes and mitigate synaptic changes post-rmTBI. Given that enrichment strategies are feasible in the clinical setting, particularly for athletes and soldiers for whom the risk of repetitive injury is greatest, these data suggest that clinical trials may be warranted.

Adolescent Mice Demonstrate a Distinct Pattern of Injury after Repetitive Mild Traumatic Brain Injury.

Recently, there has been increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI) (e.g., sports concussions). Although most of the scientific attention has focused on elite athlete populations, the sequelae of rmTBI in children and young adults have not been well studied. Prior TBI studies have suggested that developmental differences in response to injury, including differences in excitotoxicity and inflammation, could result in differences in functional and histopathological outcomes after injury. The purpose of this study is to compare outcomes in adolescent (5-week-old) versus adult (4-month-old) mice in a clinically relevant model of rmTBI. We hypothesized that functional and histopathological outcomes after rmTBI would differ in developing adolescent brains compared with mature adult brains. Male adolescent and adult (C57Bl/6) mice were subjected to a weight drop model of rmTBI (n = 10-16/group). Loss of consciousness (LOC) after each injury was measured. Functional outcomes were assessed including tests of balance (rotorod), spatial memory (Morris water maze), and impulsivity (elevated plus maze). After behavioral testing, brains were assessed for histopathological outcomes including microglial immunolabeling and N-methyl-d-aspartate (NMDA) receptor subunit expression. Injured adolescent mice had longer LOC than injured adult mice compared with their respective sham controls. Compared with sham mice, adolescent and adult mice subjected to rmTBI had impaired balance, increased impulsivity, and worse spatial memory that persisted up to 3 months after injury, and the effect of injury was worse in adolescent than in adult mice in terms of spatial memory. Three months after injury, adolescent and adult mice demonstrated increased ionized calcium binding adaptor 1 (IbA1) immunolabeling compared with sham controls. Compared with sham controls, NMDA receptor subtype 2B (NR2B) expression in the hippocampus was reduced by ∼20% in both adolescent and adult injured mice. The data suggest that injured adolescent mice may show a distinct pattern of functional deficits after injury that warrants further mechanistic studies.