Pilot feasibility and acceptability study evaluating use of group CBT-I in improving sleep and fatigue in older adults.

OBJECTIVE: This paper describes a pilot study, in a small sample of older adults, designed to ascertain the feasibility, acceptability and potential effectiveness of group Cognitive Behavioural Therapy For Insomnia (CBT-I). METHODS: Eleven older adults participated in a 3-week group CBT-I intervention with pre- and post-intervention outcome measures of sleep and fatigue. Acceptability was measured via post-intervention focus groups. Feasibility was measured via recruitment, retention and completion data. Subjective sleep outcomes were measured pre- and post-intervention using the Pittsburgh Sleep Quality Index. Fatigue was measured using the Fatigue Severity Index. Objective sleep outcome measures were obtained via pre- and post-intervention wrist actigraphy. RESULTS: Feasibility and acceptability were confirmed in the pilot study. Retention and completion levels were high, with participants largely positive in the focus group feedback. Preliminary sleep outcome data supported the potential effectiveness of the intervention in significantly improving several measures of sleep and fatigue including a three-point reduction in the Global PSQI scores, an increase in total sleep time of almost an hour per night and these results were mirrored by a significant reduction of nine points in the overall measure of fatigue severity. CONCLUSIONS: A group CBT-I intervention is a low-cost, low-risk intervention which improves subjective and objective measures of sleep in older adults. These positive sleep outcomes are translated into significantly decreased levels of fatigue. Future research should focus on a larger sample size with a randomised controlled trial design.

Evaluation of an educational program for people with dementia and their caregivers.

OBJECTIVES: This study evaluated the impact of a 5-week educational and supportive program for people newly diagnosed with dementia and their caregivers. METHODS: The study involved a pretest-posttest survey followed by interviews. Wilcoxon signed-rank test was conducted to determine postprogram changes. Kruskal-Wallis tests measured variation in responses between the people with dementia and their caregivers. Interviews were analysed using the NVivo software identifying themes against the program objectives of improving knowledge on dementia, coping strategies, communication and support services for people with dementia and their caregivers. RESULTS: Fifty-three dyads (n = 106) completed the survey. There were significant improvements in participants' level of understanding of dementia (z = -8.04, p < 0.001), knowledge of local services (z = -8.11, p < 0.001) and coping with life with dementia (z = -6.93, p < 0.001). These findings were consistent with interview data from 16 dyads. CONCLUSIONS: The increasing number of people with dementia and their caregivers living in the community present health challenges. Programs that assist this group to function well in the community are important. Evaluation of this program indicated improved outcomes in relation to adjusting to life with dementia, enhancing knowledge, fostering communication and reducing feelings of isolation. Areas of improvement included lengthening the program with ongoing contact sessions with program facilitators and other participants. Given the positive effects of the program on this vulnerable group of people, it maybe useful for health-care agencies involved in dementia care to conduct this type of program as a matter of routine treatment and care for people newly diagnosed with dementia.

The Role of Sleep Curtailment on Leptin Levels in Obesity and Diabetes Mellitus.

Emerging evidence has identified sleep as a significant, but modifiable, risk factor for metabolic syndrome, diabetes, and obesity. Leptin, an adipocyte-derived peptide and a regulator of food intake and energy expenditure, has been shown to be associated with a short sleep duration in the pathophysiology of obesity and consequently type 2 diabetes. This review focuses on the current evidence indicating the effects of a short sleep duration on the regulation of leptin concentration in association with obesity and diabetes mellitus. In summary, the evidence suggests that sleep deprivation, by affecting leptin regulation, may lead to obesity and consequently development of type 2 diabetes through increased appetite and food intake. However, findings on the role of leptin in diabetes due to sleep deprivation are contradictory, and further studies with larger sample sizes are needed to confirm previous findings.

Second-trimester maternal serum vitamin D and pregnancy outcome: The Western Australian Raine cohort study.

AIMS: To assess the effect of maternal serum 25(OH)-vitamin D levels during the second trimester of pregnancy on the risk for gestational diabetes (GDM), pregnancy and infantile outcomes. METHODS: This study is based on the Western Australian Pregnancy Cohort (Raine) study. Maternal serum 25(OH)-vitamin D concentrations of 890 pregnant women were evaluated at 18 weeks pregnancy and grouped into serum Vitamin D quartiles (>30, 30-49, 50-74 and >75 nmol/L). RESULTS: Participants with de-seasonalized 25 (OH)-vitamin D levels <30 nmol/L were more likely to develop GDM, but not after controlling for ethnicity. Women with high body mass index (BMI) >30 were at a greater risk of developing GDM. Additionally, women with GDM were at a greater risk of primary caesarean delivery. Maternal serum levels of 25(OH)-vitamin D were positively associated with birth weight, body length and head circumference of the neonate. CONCLUSION: Low maternal serum levels of 25(OH)-vitamin D are associated with GDM gestational diabetes, and race/ethnicity may modify this relationship. High pre-gestational BMI may predict GDM risk. GDM in pregnancy may increase the risk for delivery by caesarean section. Maternal 25(OH)-vitamin D is associated with anthropometric measures of the neonate.

Systematic review of clinical practice guidelines to identify recommendations for sleep in type 2 diabetes mellitus management.

INTRODUCTION: Sleep quality, quantity and timing have been shown to impact glycaemic control, with a role in insulin sensitivity, glucose tolerance and HbA1C levels, in both diabetic and non-diabetic populations. The aim of this study was to identify recommendations for sleep assessment and management in international clinical practice guidelines focused on type 2 diabetes mellitus management in adults. STUDY DESIGN: Systematic Review. METHODOLOGY: Clinical practice guidelines which focused on the management of type 2 diabetes mellitus in adults were included (n = 35). Two independent reviewers utilised the Appraisal of Guidelines for Research and Evaluation tool (AGREE) II and a third reviewer resolved any disagreements. Included guidelines were assessed for recommendations about sleep in diabetes management (n = 14). Data were extracted on sleep recommendations ,themes were generated from the extracted data and narrative syntheses were created. RESULTS: From 1114 identified papers, 35 guidelines met the inclusion criteria. Fourteen of these guidelines included recommendations pertaining to sleep, which broadly fell into five categories; sleep assessment, sleep as a therapeutic target, sleep and co-morbidities of type 2 diabetes mellitus, shift work and sleep and driving. Recommendations varied across guidelines. CONCLUSION: Few guidelines provided recommendations relating to assessment and management of sleep in type 2 diabetes care. Most of the recommendations were related to obstructive sleep apnoea. However, few guidelines discussed sleep as a therapeutic intervention for diabetes mellitus or described the potential importance of sleep quality and duration in glycaemic control. Prospero registration number: CRD42020142136.

Vitamin D and sleep duration: Is there a bidirectional relationship?

Vitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

Disrupted sleep and associated factors in Australian dementia caregivers: a cross-sectional study.

BACKGROUND: Sleep disturbance is an issue reported by caregivers. Waking at night is a feature of dementia and by proxy, sleep disturbance among caregivers is reported to be high. Little is known about the characteristics of dementia caregivers' sleep and the factors that may influence sleep disruption. The purpose of this study was to investigate the sleep characteristics and disturbances of Australian caregivers of a person living with dementia. In addition, it evaluated the psychological wellbeing of caregivers by evaluating associations between mood and sleep in this population. METHODS: This study used a cross-sectional, descriptive, correlation design. Participants were recruited with the assistance of Alzheimer's Australia, Dementia Australia and targeted social media advertising. In total, 104 adult, primary, informal caregivers of people with dementia participated, completing a questionnaire on demographic characteristics, the Depression, Anxiety and Stress Scale (DASS-21) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In this study, 76% of caregivers were female who had been caring for someone living with dementia on average for 4.8 years. 44% of participants had two or more co-morbidities namely cardiovascular disease, osteoarthritis and diabetes. 94% of participants were poor sleepers with 84% with difficulty initiating sleep and 72% reporting having difficulty maintaining sleep. Overall, psychological distress was common with high levels of moderate to severe depression, anxiety and stress. Global PSQI scores were significantly positively associated with depression and anxiety, with the strongest correlation seen with stress scores. Depression scores were also moderately associated with daytime dysfunction. Stress was identified as a significant predictor of overall sleep quality. CONCLUSIONS: Sleep problems are common within the population of dementia caregivers. Due to the nature and duration of caregiving and the progression of dementia of the care recipient, there is the potential for a decline in the caregivers' mental and physical health. Caregivers of those living with dementia are more likely to have comorbidities, depression, anxiety and stress. Sleep quality is correlated with emotional distress in dementia caregivers although the direction of this association is unclear. Therefore, sleep and psychological wellbeing may be intertwined, with improvements in one aspect resulting in a positive impact in the other.

Subcellular Localization of NR4A2 Orphan Nuclear Receptor Expression in Human and Mouse Synovial Joint Tissue.

NR4A1-3 receptors are required in inflammatory disease initiation and progression, where they function as early response regulators, controlling the extent of the inflammatory response and promoting inflammatory resolution. NR4A receptor activity controls inflammatory processes in several diseases characterized by chronic inflammation including rheumatoid arthritis (RA) and atherosclerosis. Studies indicate that cell-type and cellular microenvironment can alter NR4A1-3 receptor activity and influence their biological roles. Thus, the study of appropriate in vivo models of inflammatory disease is important to ascertain their cell- and tissue-specific functional roles. Here we describe immunohistochemical approaches optimized to study the expression patterns of NR4A nuclear receptors in inflamed synovium tissues obtained from patients diagnosed with RA and mouse models of inflammatory joint disease.

Adjuvant Corticosteroid Therapy for Acute Bacterial Meningitis.

Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library.

Effective masking levels for 500 and 2000 Hz bone conduction auditory steady state responses in infants and adults with normal hearing.

OBJECTIVES: Few studies have investigated effective masking levels (EMLs) needed to isolate the test ear for bone conduction assessments in infants. The objective of this study was to determine EMLs for 500 and 2000 Hz bone conduction auditory steady state responses (ASSRs) to amplitude (AM)/frequency-modulated (FM) stimuli for infants and adults with normal hearing. Maturational factors that contribute to infant-adult differences in EMLs will also be investigated. The present study and previously published 1000 and 4000 Hz EML data will be compared to investigate EML across four frequencies. These findings will provide a starting point for implementing clinical masking for infant bone conduction testing using physiological measures. DESIGN: Participants were 15 infants (7 to 35 weeks) and 15 adults (21 to 56 years) with normal hearing. Bone-conducted single ASSR stimuli (research MASTER) were 100% AM and 25% FM at 85 and 101 Hz for 500 and 2000 Hz carrier frequencies, respectively. They were presented at 25 and 35 dB HL for 500 Hz and at 35 and 45 dB HL for 2000 Hz for both infants and adults (approximately 10 and 20 dB SL at each frequency for infants). Air-conducted narrowband maskers were presented to both ears simultaneously. Real-ear to coupler differences were measured to account for differences in the sound pressure developed in infant and adult ear canals as a result of ear-canal size. Data analyses were conducted for mean EMLs across frequency (500 to 4000 Hz) and between age groups. Masked and unmasked ASSR amplitudes were compared for 500 and 2000 Hz. RESULTS: Both infants and adults required much more masking (25 to 33 dB) to eliminate responses at 500 compared with 2000 Hz. On average, infants required 16 dB more masking at 500 Hz and similar amounts of masking at 2000 Hz compared with adults. When adjusted for ear-canal size and bone conduction sensitivity, the pattern of results did not change. Across all four frequencies, infants showed a systematic decrease in mean EMLs with an increase in frequency; all pair-wise comparisons were significant except 2000 versus 4000 Hz. Adults showed smaller frequency-dependent changes in EML (only significantly greater for 500 versus 2000 Hz and 4000 Hz). When ear-canal size and bone conduction sensitivity were taken into account, only 500 Hz required more masking than other frequencies in infants; there were no significant frequency-dependent trends for adults, although the greater EMLs at 1000 versus 2000 Hz and 4000 Hz approached significance. Unmasked and masked amplitudes tended to be larger for 2000 Hz but not for 500 Hz when comparing infants with adults. CONCLUSIONS: EMLs appropriate for infants for bone conduction ASSRs elicited to AM/FM stimuli are considerably higher at 500 compared with 2000 Hz. Infants also need more masking at 500 Hz compared with adults but the same amount of masking at 2000 Hz. Comparisons across four frequencies reveal a systematic decrease in EML with an increase in frequency in infants, which is not apparent in adults. Recommended EMLs for AM/FM bone-conducted ASSR stimuli presented at 35 dB HL for 500, 1000, 2000, and 4000 Hz, respectively, are: (1) infants: 81, 68, 59, and 45 dB SPL, and (2) adults: 66, 63, 59, and 55 dB SPL.

Tumor necrosis factor inhibition modulates thrombospondin-1 expression in human inflammatory joint disease through altered NR4A2 activity.

We examined thrombospondin-1 (THBS1, alias TSP-1) expression in human synovial tissue (ST) during the resolution phase of chronic inflammation and elucidated its transcriptional regulation by the orphan receptor 4A2 (NR4A2). In vivo, rheumatoid arthritis (RA) serum and ST revealed altered expression levels and tissue distribution of TSP-1. After anti-tumor necrosis factor therapy, a reciprocal relationship between TSP-1 and NR4A2 expression levels was measured in patients with clinical and ST responses to biological treatment. In vitro, primary RA fibroblast-like synoviocytes (FLSs) expressed minimal TSP-1 mRNA levels with high transcript levels of NR4A2, vascular endothelial growth factor (VEGF), and IL-8 measured. Hypoxic modulation of RA FLSs resulted in inverse expression levels of TSP-1 compared with NR4A2, IL-8, and VEGF. Ectopic NR4A2 expression led to reduced TSP-1 mRNA and protein levels with concomitant increases in proangiogenic mediators. NR4A2 transcriptional activity, independent of DNA binding, repressed the hTSP-1 promoter leading to reduced mRNA and protein release in immortalized K4IM FLSs. Bioinformatic and deletion studies identified a 5' region of the TSP-1 promoter repressed by NR4A2 and proangiogenic transcription factors, including NF-κB and Ets1/2. Stable depletion of NR4A2 levels resulted in a shift in the TSP-1/VEGF expression ratio. Thus, modulation of TSP-1 expression is achieved through anti-tumor necrosis factor therapy effects on specific transcriptional networks, suggesting that enhanced TSP-1 expression may help restore tissue homeostasis during resolution of inflammation.

Orphan nuclear receptor NR4A2 induces synoviocyte proliferation, invasion, and matrix metalloproteinase 13 transcription.

OBJECTIVE: To address the role of the nuclear receptor 4A (NR4A) family of orphan nuclear receptors in synoviocyte transformation, hyperplasia, and regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in models of inflammatory arthritis. METHODS: NR4A messenger RNA levels in synovial tissue and primary synoviocytes were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). NR4A2 was stably overexpressed in normal synoviocytes, and cell proliferation, survival, anchorage-independent growth, migration, and invasion were monitored in vitro. MMP and TIMP expression levels were analyzed by quantitative RT-PCR, and MMP-13 promoter activity was measured using reporter assays. Stable depletion of endogenous NR4A levels was achieved by lentiviral transduction of NR4A short hairpin RNA (shRNA), and the effects on proliferation, migration, and MMP-13 expression were analyzed. RESULTS: NR4A2 was expressed at elevated levels in normal, OA, and RA synovial tissue and in primary RA synoviocytes. Tumor necrosis factor α (TNFα) rapidly and selectively induced expression of NR4A2 in synoviocytes. Ectopic expression of NR4A2 in normal synoviocytes significantly increased proliferation and survival, promoted anchorage-independent growth, and induced migration and invasion. MMP-13 gene expression was synergistically induced by NR4A2 and TNFα, while expression of TIMP-2 was antagonized. NR4A2 directly transactivated the proximal MMP-13 promoter, and a point mutation in the DNA binding domain of NR4A2 abolished transcriptional activation. Depletion of endogenous NR4A receptors with shRNA reduced synoviocyte proliferation, migration, and MMP-13 expression. CONCLUSION: The orphan nuclear receptor NR4A2 is a downstream mediator of TNFα signaling in synovial tissue. NR4A2 transcriptional activity contributes to the hyperplastic and invasive phenotype of synoviocytes that leads to cartilage destruction, suggesting that this receptor may show promise as a therapeutic target in inflammatory arthritis.

DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory.

Deficiency in the guanine nucleotide exchange factor dedicator of cytokinesis 8 (DOCK8) causes a human immunodeficiency syndrome associated with recurrent sinopulmonary and viral infections. We have recently identified a DOCK8-deficient mouse strain, carrying an ethylnitrosourea-induced splice-site mutation that shows a failure to mature a humoral immune response due to the loss of germinal centre B cells. In this study, we turned to T-cell immunity to investigate further the human immunodeficiency syndrome and its association with decreased peripheral CD4(+) and CD8(+) T cells. Characterisation of the DOCK8-deficient mouse revealed T-cell lymphopenia, with increased T-cell turnover and decreased survival. Egress of mature CD4(+) thymocytes was reduced with increased migration of these cells to the chemokine CXCL12. However, despite the two-fold reduction in peripheral naïve T cells, the DOCK8-deficient mice generated a normal primary CD8(+) immune response and were able to survive acute influenza virus infection. The limiting effect of DOCK8 was in the normal survival of CD8(+) memory T cells after infection. These findings help to explain why DOCK8-deficient patients are susceptible to recurrent infections and provide new insights into how T-cell memory is sustained.